chr1-243256127-T-A

Variant names:

• chr1-243256127-T-A
• rs3904682
• NM_006642.5:c.-47T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006642.5(SDCCAG8):​c.-47T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,563,582 control chromosomes in the GnomAD database, including 204,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (16060 hom., cov: 33)
  • Exomes 𝑓: 0.51 (188213 hom.)
• Consequence: SDCCAG8 NM_006642.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.67
• Publications: 21 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-243256127-T-A is Benign according to our data. Variant chr1-243256127-T-A is described in ClinVar as [Benign]. Clinvar id is 260005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.-47T>A		5_prime_UTR_variant	Exon 1 of 18	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.-47T>A		5_prime_UTR_variant	Exon 1 of 18	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000490065.5	n.94T>A		non_coding_transcript_exon_variant	Exon 1 of 5	4

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63615 AN: 152026 Hom.: 16038 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.500 AC: 125641 AN: 251130 AF XY: 0.494

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.466

Gnomad EAS exome AF: 0.733

Gnomad FIN exome AF: 0.545

Gnomad NFE exome AF: 0.514

Gnomad OTH exome AF: 0.506

GnomAD4 exome AF: 0.508 AC: 716456 AN: 1411438 Hom.: 188213 Cov.: 24 AF XY: 0.502 AC XY: 354204 AN XY: 705442

African (AFR) AF: 0.107 AC: 3470 AN: 32546

American (AMR) AF: 0.618 AC: 27612 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12096 AN: 25770

East Asian (EAS) AF: 0.752 AC: 29660 AN: 39438

South Asian (SAS) AF: 0.348 AC: 29671 AN: 85284

European-Finnish (FIN) AF: 0.541 AC: 28852 AN: 53330

Middle Eastern (MID) AF: 0.435 AC: 2467 AN: 5670

European-Non Finnish (NFE) AF: 0.519 AC: 552888 AN: 1066108

Other (OTH) AF: 0.507 AC: 29740 AN: 58634

GnomAD4 genome AF: 0.418 AC: 63648 AN: 152144 Hom.: 16060 Cov.: 33 AF XY: 0.422 AC XY: 31381 AN XY: 74388

African (AFR) AF: 0.125 AC: 5204 AN: 41518

American (AMR) AF: 0.578 AC: 8840 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3470

East Asian (EAS) AF: 0.740 AC: 3831 AN: 5174

South Asian (SAS) AF: 0.349 AC: 1684 AN: 4828

European-Finnish (FIN) AF: 0.537 AC: 5680 AN: 10582

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35177 AN: 67962

Other (OTH) AF: 0.472 AC: 995 AN: 2110

Alfa AF: 0.379 Hom.: 1937

Bravo AF: 0.413

Asia WGS AF: 0.527 AC: 1832 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Senior-Loken syndrome 7 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Bardet-Biedl syndrome 16 Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		1.7
PromoterAI		0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=296/4	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: rs3904682; hg19: chr1-243419429; COSMIC: COSV59412140; COSMIC: COSV59412140;