rs10926984

Variant names:

• chr1-243298851-T-G
• rs10926984
• NM_006642.5:c.675+5632T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006642.5(SDCCAG8):​c.675+5632T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,254 control chromosomes in the GnomAD database, including 1,204 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1204 hom., cov: 31)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.996
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 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.675+5632T>G		intron	N/A	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.771+5357T>G		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.381+5632T>G		intron	N/A	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.675+5632T>G		intron	N/A	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000435549.1	TSL:1	c.16-5862T>G		intron	N/A	ENSP00000410200.1	A0A0C4DG71
	SDCCAG8	ENST00000884080.1		c.771+5357T>G		intron	N/A	ENSP00000554139.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16721 AN: 152136 Hom.: 1204 Cov.: 31

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.0674

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.110 AC: 16721 AN: 152254 Hom.: 1204 Cov.: 31 AF XY: 0.109 AC XY: 8080 AN XY: 74444

African (AFR) AF: 0.0294 AC: 1221 AN: 41574

American (AMR) AF: 0.130 AC: 1991 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 324 AN: 3466

East Asian (EAS) AF: 0.0673 AC: 349 AN: 5184

South Asian (SAS) AF: 0.108 AC: 520 AN: 4828

European-Finnish (FIN) AF: 0.132 AC: 1401 AN: 10592

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10444 AN: 68006

Other (OTH) AF: 0.109 AC: 230 AN: 2110

Alfa AF: 0.136 Hom.: 1769

Bravo AF: 0.106

Asia WGS AF: 0.0650 AC: 226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.80
PhyloP100		1.0
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: rs10926984; hg19: chr1-243462153;