1-243256127-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):

• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• ciliopathy

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• 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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	NM_006642.5	MANE Select	c.-47T>A		5_prime_UTR	Exon 1 of 18	NP_006633.1	Q86SQ7-1
	SDCCAG8	NM_001350248.2		c.-47T>A		5_prime_UTR	Exon 1 of 19	NP_001337177.1
	SDCCAG8	NM_001350249.2		c.-354T>A		5_prime_UTR	Exon 1 of 18	NP_001337178.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SDCCAG8	ENST00000366541.8	TSL:1 MANE Select	c.-47T>A		5_prime_UTR	Exon 1 of 18	ENSP00000355499.3	Q86SQ7-1
	SDCCAG8	ENST00000884080.1		c.-47T>A		5_prime_UTR	Exon 1 of 19	ENSP00000554139.1
	SDCCAG8	ENST00000951623.1		c.-47T>A		5_prime_UTR	Exon 1 of 18	ENSP00000621682.1

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Bardet-Biedl syndrome 16 (2)
-	-	2	not provided (2)
-	-	2	Senior-Loken syndrome 7 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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;