rs137903012

chr1-243316734-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006642.5(SDCCAG8):c.930-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,613,824 control chromosomes in the GnomAD database, including 464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (33 hom., cov: 33)
  • Exomes 𝑓: 0.020 (431 hom.)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.437

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-243316734-A-G is Benign according to our data. Variant chr1-243316734-A-G is described in ClinVar as [Benign]. Clinvar id is 260014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243316734-A-G is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCCAG8	NM_006642.5	c.930-21A>G		intron_variant		ENST00000366541.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.930-21A>G		intron_variant		1	NM_006642.5	P1
SDCCAG8	ENST00000435549.1	c.270-21A>G		intron_variant		1
SDCCAG8	ENST00000463012.1	n.290-21A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2214 AN: 152078 Hom.: 35 Cov.: 33

Gnomad AFR AF: 0.00394

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.00528

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0205

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.0189 AC: 4743 AN: 251122 Hom.: 90 AF XY: 0.0218 AC XY: 2965 AN XY: 135808

Gnomad AFR exome AF: 0.00291

Gnomad AMR exome AF: 0.0107

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0505

Gnomad FIN exome AF: 0.00499

Gnomad NFE exome AF: 0.0202

Gnomad OTH exome AF: 0.0247

GnomAD4 exome AF: 0.0198 AC: 28987 AN: 1461628 Hom.: 431 Cov.: 32 AF XY: 0.0214 AC XY: 15529 AN XY: 727124

Gnomad4 AFR exome AF: 0.00317

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0534

Gnomad4 FIN exome AF: 0.00541

Gnomad4 NFE exome AF: 0.0193

Gnomad4 OTH exome AF: 0.0199

GnomAD4 genome AF: 0.0145 AC: 2208 AN: 152196 Hom.: 33 Cov.: 33 AF XY: 0.0144 AC XY: 1071 AN XY: 74438

Gnomad4 AFR AF: 0.00390

Gnomad4 AMR AF: 0.0148

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.00528

Gnomad4 NFE AF: 0.0205

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0178 Hom.: 7

Bravo AF: 0.0133

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	3.4
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.36		Position offset: 21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs137903012; hg19: chr1-243480036; COSMIC: COSV59411133;