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):

• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006642.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.1725G>A	p.Glu575Glu	synonymous	Exon 14 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.1821G>A	p.Glu607Glu	synonymous	Exon 15 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1431G>A	p.Glu477Glu	synonymous	Exon 14 of 18	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.1725G>A	p.Glu575Glu	synonymous	Exon 14 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.957-10617G>A		intron	N/A	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000884080.1		c.1821G>A	p.Glu607Glu	synonymous	Exon 15 of 19	ENSP00000554139.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Senior-Loken syndrome 7 (3)
-	-	2	Bardet-Biedl syndrome 16 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 (1)

Computational scores

Source: dbNSFP v4.9

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;