1-243445665-A-G

Variant names:

• chr1-243445665-A-G
• rs6703335
• NM_006642.5:c.1985+19107A>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.1985+19107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,012 control chromosomes in the GnomAD database, including 20,794 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 0.50 (20794 hom., cov: 32)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 26 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 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.1985+19107A>G		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.2081+19107A>G		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1691+19107A>G		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.1985+19107A>G		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.1088+19107A>G		intron	N/A	ENSP00000410200.1
	SDCCAG8	ENST00000463042.1	TSL:2	n.192+19107A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76584 AN: 151892 Hom.: 20789 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.504 AC: 76603 AN: 152012 Hom.: 20794 Cov.: 32 AF XY: 0.504 AC XY: 37455 AN XY: 74282

African (AFR) AF: 0.300 AC: 12447 AN: 41470

American (AMR) AF: 0.620 AC: 9472 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1976 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4038 AN: 5166

South Asian (SAS) AF: 0.440 AC: 2117 AN: 4814

European-Finnish (FIN) AF: 0.559 AC: 5901 AN: 10558

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38903 AN: 67952

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.553 Hom.: 74235

Bravo AF: 0.500

Asia WGS AF: 0.591 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.82
PhyloP100		0.38
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: rs6703335; hg19: chr1-243608967;