rs976529

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_006642.5(SDCCAG8):c.912C>T(p.Thr304Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 1,614,026 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.028 ( 644 hom. )

Consequence

SDCCAG8
NM_006642.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.48

Publications

7 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 1-243308160-C-T is Benign according to our data. Variant chr1-243308160-C-T is described in ClinVar as Benign. ClinVar VariationId is 260013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0206 (3134/152268) while in subpopulation NFE AF = 0.0315 (2145/68022). AF 95% confidence interval is 0.0304. There are 49 homozygotes in GnomAd4. There are 1449 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5 link	c.912C>T	p.Thr304Thr	synonymous_variant	Exon 8 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SDCCAG8	ENST00000366541.8 link	c.912C>T	p.Thr304Thr	synonymous_variant	Exon 8 of 18	1	NM_006642.5	ENSP00000355499.3	Q86SQ7-1
SDCCAG8	ENST00000435549.1 link	c.252C>T	p.Thr84Thr	synonymous_variant	Exon 3 of 11	1		ENSP00000410200.1	A0A0C4DG71
SDCCAG8	ENST00000463012.1 link	n.272C>T		non_coding_transcript_exon_variant	Exon 2 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3135

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00495

Gnomad AMI

AF:

0.0692

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0315

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.0201

AC:

5064

AN:

251390

AF XY:

0.0205

show subpopulations

Gnomad AFR exome

AF:

0.00541

Gnomad AMR exome

AF:

0.0160

Gnomad ASJ exome

AF:

0.00962

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0154

Gnomad NFE exome

AF:

0.0324

Gnomad OTH exome

AF:

0.0240

GnomAD4 exome

AF:

0.0275

AC:

40206

AN:

1461758

Hom.:

644

Cov.:

AF XY:

0.0270

AC XY:

19602

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00469

AC:

157

AN:

33480

American (AMR)

AF:

0.0175

AC:

782

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

256

AN:

26132

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00664

AC:

573

AN:

86254

European-Finnish (FIN)

AF:

0.0189

AC:

1008

AN:

53390

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0323

AC:

35924

AN:

1111932

Other (OTH)

AF:

0.0238

AC:

1437

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

2113

4225

6338

8450

10563

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1334

2668

4002

5336

6670

<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:

0.0206

AC:

3134

AN:

152268

Hom.:

Cov.:

AF XY:

0.0195

AC XY:

1449

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00491

AC:

204

AN:

41566

American (AMR)

AF:

0.0284

AC:

435

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00663

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0137

AC:

145

AN:

10594

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0315

AC:

2145

AN:

68022

Other (OTH)

AF:

0.0223

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

163

326

489

652

815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0278

Hom.:

131

Bravo

AF:

0.0217

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0293

EpiControl

AF:

0.0321

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Senior-Loken syndrome 7

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Bardet-Biedl syndrome 16

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kidney disorder

Benign:1

Feb 01, 2018

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.3

(source)

DANN

Benign

0.68

PhyloP100

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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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