rs398050192

Variant names:

• chr1-243344378-C-CA
• rs398050192
• NM_006642.5:c.1473+48dupA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_006642.5(SDCCAG8):​c.1473+48dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,194,606 control chromosomes in the GnomAD database, including 47,252 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5333 hom., cov: 24)
  • Exomes 𝑓: 0.27 (41919 hom.)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0960
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 1-243344378-C-CA is Benign according to our data. Variant chr1-243344378-C-CA is described in ClinVar as Benign. ClinVar VariationId is 260008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.338 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.1473+48dupA		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.1569+48dupA		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.1179+48dupA		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.1473+47_1473+48insA		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.813+47_813+48insA		intron	N/A	ENSP00000410200.1
	SDCCAG8	ENST00000493334.1	TSL:5	n.440+47_440+48insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39751 AN: 151938 Hom.: 5330 Cov.: 24

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.253 AC: 63042 AN: 248724 AF XY: 0.267

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.0388

Gnomad FIN exome AF: 0.253

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.272

GnomAD4 exome AF: 0.271 AC: 282697 AN: 1042550 Hom.: 41919 Cov.: 14 AF XY: 0.277 AC XY: 149136 AN XY: 537912

African (AFR) AF: 0.273 AC: 6898 AN: 25234

American (AMR) AF: 0.139 AC: 6124 AN: 44124

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6040 AN: 23580

East Asian (EAS) AF: 0.0247 AC: 932 AN: 37768

South Asian (SAS) AF: 0.364 AC: 28239 AN: 77664

European-Finnish (FIN) AF: 0.258 AC: 13748 AN: 53222

Middle Eastern (MID) AF: 0.367 AC: 1819 AN: 4954

European-Non Finnish (NFE) AF: 0.283 AC: 206236 AN: 729396

Other (OTH) AF: 0.272 AC: 12661 AN: 46608

GnomAD4 genome AF: 0.262 AC: 39772 AN: 152056 Hom.: 5333 Cov.: 24 AF XY: 0.261 AC XY: 19377 AN XY: 74338

African (AFR) AF: 0.269 AC: 11154 AN: 41486

American (AMR) AF: 0.196 AC: 3003 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3466

East Asian (EAS) AF: 0.0339 AC: 176 AN: 5194

South Asian (SAS) AF: 0.352 AC: 1692 AN: 4804

European-Finnish (FIN) AF: 0.246 AC: 2597 AN: 10556

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19313 AN: 67944

Other (OTH) AF: 0.260 AC: 549 AN: 2108

Alfa AF: 0.282 Hom.: 1302

Bravo AF: 0.255

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Bardet-Biedl syndrome 16 (1)
-	-	1	not specified (1)
-	-	1	Senior-Loken syndrome 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.096
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: rs398050192; hg19: chr1-243507680; COSMIC: COSV107413647; COSMIC: COSV107413647;