rs10927011

Variant names:

• chr1-243415810-G-A
• rs10927011
• NM_006642.5:c.1725G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-243415810-G-A
• chr1-243415810-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006642.5(SDCCAG8):​c.1725G>A​(p.Glu575Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,612,870 control chromosomes in the GnomAD database, including 205,353 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (15777 hom., cov: 33)
  • Exomes 𝑓: 0.50 (189576 hom.)
• Consequence: SDCCAG8 NM_006642.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.55
• Publications: 23 publications found

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-243415810-G-A is Benign according to our data. Variant chr1-243415810-G-A is described in ClinVar as Benign. ClinVar VariationId is 260009.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.1725G>A	p.Glu575Glu	synonymous_variant	Exon 14 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1725G>A	p.Glu575Glu	synonymous_variant	Exon 14 of 18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000435549.1	c.957-10617G>A		intron_variant	Intron 8 of 10	1		ENSP00000410200.1
SDCCAG8	ENST00000493334.1	n.692G>A		non_coding_transcript_exon_variant	Exon 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63995 AN: 151982 Hom.: 15777 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.778

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.461

GnomAD2 exomes AF: 0.500 AC: 124877 AN: 249974 AF XY: 0.497

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.584

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.768

Gnomad FIN exome AF: 0.515

Gnomad NFE exome AF: 0.501

Gnomad OTH exome AF: 0.501

GnomAD4 exome AF: 0.503 AC: 734612 AN: 1460770 Hom.: 189576 Cov.: 51 AF XY: 0.500 AC XY: 363494 AN XY: 726648

African (AFR) AF: 0.137 AC: 4567 AN: 33434

American (AMR) AF: 0.576 AC: 25657 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13444 AN: 26106

East Asian (EAS) AF: 0.774 AC: 30719 AN: 39686

South Asian (SAS) AF: 0.420 AC: 36199 AN: 86232

European-Finnish (FIN) AF: 0.507 AC: 27070 AN: 53380

Middle Eastern (MID) AF: 0.505 AC: 2882 AN: 5710

European-Non Finnish (NFE) AF: 0.507 AC: 563580 AN: 1111328

Other (OTH) AF: 0.505 AC: 30494 AN: 60334

GnomAD4 genome AF: 0.421 AC: 64005 AN: 152100 Hom.: 15777 Cov.: 33 AF XY: 0.425 AC XY: 31574 AN XY: 74362

African (AFR) AF: 0.159 AC: 6582 AN: 41498

American (AMR) AF: 0.548 AC: 8371 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1771 AN: 3470

East Asian (EAS) AF: 0.778 AC: 4024 AN: 5172

South Asian (SAS) AF: 0.415 AC: 2002 AN: 4828

European-Finnish (FIN) AF: 0.522 AC: 5518 AN: 10572

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34215 AN: 67962

Other (OTH) AF: 0.465 AC: 982 AN: 2112

Alfa AF: 0.479 Hom.: 74779

Bravo AF: 0.411

Asia WGS AF: 0.567 AC: 1973 AN: 3478

EpiCase AF: 0.498

EpiControl AF: 0.502

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Senior-Loken syndrome 7 Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Bardet-Biedl syndrome 16 Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10927011; hg19: chr1-243579112; COSMIC: COSV100653902; COSMIC: COSV100653902;