1-243316734-A-G

Variant names:

• chr1-243316734-A-G
• rs137903012
• NM_006642.5:c.930-21A>G

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.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:3
• Conservation: PhyloP100: 0.437
• 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 1-243316734-A-G is Benign according to our data. Variant chr1-243316734-A-G is described in ClinVar as Benign. ClinVar VariationId is 260014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0533 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.930-21A>G		intron	N/A	NP_006633.1
	SDCCAG8	NM_001350248.2		c.1026-21A>G		intron	N/A	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.636-21A>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.930-21A>G		intron	N/A	ENSP00000355499.3
	SDCCAG8	ENST00000435549.1	TSL:1	c.270-21A>G		intron	N/A	ENSP00000410200.1
	SDCCAG8	ENST00000463012.1	TSL:2	n.290-21A>G		intron	N/A

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

GnomAD2 exomes AF: 0.0189 AC: 4743 AN: 251122 AF XY: 0.0218

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 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

African (AFR) AF: 0.00317 AC: 106 AN: 33474

American (AMR) AF: 0.0110 AC: 490 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0207 AC: 542 AN: 26134

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39688

South Asian (SAS) AF: 0.0534 AC: 4608 AN: 86244

European-Finnish (FIN) AF: 0.00541 AC: 289 AN: 53406

Middle Eastern (MID) AF: 0.0584 AC: 337 AN: 5768

European-Non Finnish (NFE) AF: 0.0193 AC: 21407 AN: 1111820

Other (OTH) AF: 0.0199 AC: 1203 AN: 60374

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

African (AFR) AF: 0.00390 AC: 162 AN: 41500

American (AMR) AF: 0.0148 AC: 227 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0485 AC: 234 AN: 4822

European-Finnish (FIN) AF: 0.00528 AC: 56 AN: 10600

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0205 AC: 1393 AN: 68000

Other (OTH) AF: 0.0161 AC: 34 AN: 2114

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.4
DANN	Benign	0.71
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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