NM_006642.5:c.1616+2662C>G

Variant names:

• chr1-243381525-C-G
• rs1538774
• NM_006642.5:c.1616+2662C>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.1616+2662C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 151,880 control chromosomes in the GnomAD database, including 45,922 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 0.78 (45922 hom., cov: 30)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.1616+2662C>G		intron_variant	Intron 13 of 17	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1616+2662C>G		intron_variant	Intron 13 of 17	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000435549.1	c.956+2662C>G		intron_variant	Intron 8 of 10	1		ENSP00000410200.1
SDCCAG8	ENST00000493334.1	n.583+2662C>G		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117888 AN: 151762 Hom.: 45870 Cov.: 30

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.968

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.791

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

GnomAD4 genome AF: 0.777 AC: 117999 AN: 151880 Hom.: 45922 Cov.: 30 AF XY: 0.776 AC XY: 57594 AN XY: 74230

African (AFR) AF: 0.783 AC: 32471 AN: 41450

American (AMR) AF: 0.848 AC: 12938 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 2687 AN: 3462

East Asian (EAS) AF: 0.968 AC: 4976 AN: 5140

South Asian (SAS) AF: 0.667 AC: 3216 AN: 4818

European-Finnish (FIN) AF: 0.761 AC: 8015 AN: 10530

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51166 AN: 67908

Other (OTH) AF: 0.792 AC: 1672 AN: 2110

Alfa AF: 0.694 Hom.: 2260

Bravo AF: 0.788

Asia WGS AF: 0.790 AC: 2746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		-0.18
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: rs1538774; hg19: chr1-243544827;