1-243299065-G-A

Variant names:

• chr1-243299065-G-A
• rs2484639
• NM_006642.5:c.676-5648G>A

Variant summary

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

The NM_006642.5(SDCCAG8):​c.676-5648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,028 control chromosomes in the GnomAD database, including 17,336 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 0.45 (17336 hom., cov: 33)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.722 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.676-5648G>A		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.771+5571G>A		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.382-5648G>A		intron	N/A	NP_001337178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.676-5648G>A		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.16-5648G>A		intron	N/A	ENSP00000410200.1
	SDCCAG8	ENST00000476722.6	TSL:3	c.267+5571G>A		intron	N/A	ENSP00000473868.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 69007 AN: 151910 Hom.: 17315 Cov.: 33

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.454 AC: 69046 AN: 152028 Hom.: 17336 Cov.: 33 AF XY: 0.458 AC XY: 34025 AN XY: 74308

African (AFR) AF: 0.230 AC: 9546 AN: 41460

American (AMR) AF: 0.583 AC: 8909 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3468

East Asian (EAS) AF: 0.742 AC: 3835 AN: 5168

South Asian (SAS) AF: 0.365 AC: 1761 AN: 4824

European-Finnish (FIN) AF: 0.584 AC: 6169 AN: 10562

Middle Eastern (MID) AF: 0.452 AC: 132 AN: 292

European-Non Finnish (NFE) AF: 0.523 AC: 35530 AN: 67948

Other (OTH) AF: 0.492 AC: 1041 AN: 2114

Alfa AF: 0.504 Hom.: 18314

Bravo AF: 0.446

Asia WGS AF: 0.542 AC: 1879 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.13
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: rs2484639; hg19: chr1-243462367;