chr1-243330605-A-T

Position:

chr1-243330605-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006642.5(SDCCAG8):c.1134A>T(p.Glu378Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,592 control chromosomes in the GnomAD database, including 75,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5461 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69937 hom. )

Consequence

SDCCAG8
NM_006642.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.125

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00143978).

BP6

Variant 1-243330605-A-T is Benign according to our data. Variant chr1-243330605-A-T is described in ClinVar as [Benign]. Clinvar id is 260006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243330605-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SDCCAG8	NM_006642.5 link	c.1134A>T	p.Glu378Asp	missense_variant	10/18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8 link	c.1134A>T	p.Glu378Asp	missense_variant	10/18	1	NM_006642.5	ENSP00000355499.3		Q86SQ7-1
SDCCAG8	ENST00000435549.1 link	c.474A>T	p.Glu158Asp	missense_variant	5/11	1		ENSP00000410200.1		A0A0C4DG71

Frequencies

GnomAD3 genomes

AF:

0.262

AC:

39858

AN:

151898

Hom.:

5463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.308

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.350

Gnomad NFE

AF:

0.299

Gnomad OTH

AF:

0.265

GnomAD3 exomes

AF:

0.294

AC:

73899

AN:

251280

Hom.:

11830

AF XY:

0.308

AC XY:

41779

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.196

Gnomad SAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.282

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.304

AC:

444396

AN:

1461576

Hom.:

69937

Cov.:

AF XY:

0.311

AC XY:

225884

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.193

Gnomad4 AMR exome

AF:

0.199

Gnomad4 ASJ exome

AF:

0.353

Gnomad4 EAS exome

AF:

0.188

Gnomad4 SAS exome

AF:

0.454

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.304

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.262

AC:

39851

AN:

152016

Hom.:

5461

Cov.:

AF XY:

0.264

AC XY:

19650

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.194

Gnomad4 AMR

AF:

0.214

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.186

Gnomad4 SAS

AF:

0.455

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.299

Gnomad4 OTH

AF:

0.264

Alfa

AF:

0.268

Hom.:

1789

Bravo

AF:

0.252

TwinsUK

AF:

0.307

AC:

1138

ALSPAC

AF:

0.304

AC:

1172

ESP6500AA

AF:

0.191

AC:

843

ESP6500EA

AF:

0.308

AC:

2645

ExAC

AF:

0.297

AC:

36107

Asia WGS

AF:

0.322

AC:

1121

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Senior-Loken syndrome 7

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Bardet-Biedl syndrome 16

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.66

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.16

Sift

Benign

0.14

T;T

Sift4G

Benign

0.089

T;D

Polyphen

0.12

B;.

Vest4

0.17

MutPred

0.023

Gain of MoRF binding (P = 0.0851);.;

MPC

0.052

ClinPred

0.016

GERP RS

0.25

Varity_R

0.13

gMVP

0.16

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over