rs115098969

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006642.5(SDCCAG8):c.1094G>A(p.Arg365Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,614,050 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R365T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 3 hom. )

Consequence

SDCCAG8
NM_006642.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 1.19

Publications

1 publications found

Variant links:

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

SDCCAG8 Gene-Disease associations (from GenCC):

Senior-Loken syndrome 7
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Bardet-Biedl syndrome 16
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
Bardet-Biedl syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SDCCAG8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002281934).

BP6

Variant 1-243330565-G-A is Benign according to our data. Variant chr1-243330565-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 193691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00208 (316/152204) while in subpopulation AFR AF = 0.0073 (303/41506). AF 95% confidence interval is 0.00662. There are 1 homozygotes in GnomAd4. There are 151 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5 link	c.1094G>A	p.Arg365Lys	missense_variant	Exon 10 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8 link	c.1094G>A	p.Arg365Lys	missense_variant	Exon 10 of 18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000435549.1 link	c.434G>A	p.Arg145Lys	missense_variant	Exon 5 of 11	1		ENSP00000410200.1

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000525

AC:

132

AN:

251400

AF XY:

0.000420

show subpopulations

Gnomad AFR exome

AF:

0.00702

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000168

AC:

245

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00591

AC:

198

AN:

33480

American (AMR)

AF:

0.000425

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000540

AC:

AN:

1111976

Other (OTH)

AF:

0.000315

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00208

AC:

316

AN:

152204

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00730

AC:

303

AN:

41506

American (AMR)

AF:

0.000523

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68010

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000796

Hom.:

Bravo

AF:

0.00222

ESP6500AA

AF:

0.00749

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 30, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Mar 05, 2015

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 20, 2021

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SDCCAG8-related disorder

Benign:1

Jun 19, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Aug 26, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16

Benign:1

Jan 12, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.3

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.65

.;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.5

N;.

PhyloP100

1.2

PrimateAI

Benign

0.31

PROVEAN

Benign

0.82

N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.075

MVP

0.20

MPC

0.040

ClinPred

0.0010

GERP RS

2.0

Varity_R

0.045

gMVP

0.039

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over