rs731947

chr10-133459959-C-Gchr10-133459959-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001396050.1(SCART1):c.1758C>G(p.Asp586Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 542,090 control chromosomes in the GnomAD database, including 196,214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (46894 hom., cov: 35)
  • Exomes 𝑓: 0.87 (149320 hom.)
• Consequence: SCART1 NM_001396050.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

Genes affected

SCART1 (HGNC:32411): (scavenger receptor family member expressed on T cells 1) Predicted to enable scavenger receptor activity. Predicted to be involved in endocytosis. Located in brush border and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.109885E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCART1	NM_001396050.1	c.1758C>G	p.Asp586Glu	missense_variant	6/12	ENST00000640237.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCART1	ENST00000640237.2	c.1758C>G	p.Asp586Glu	missense_variant	6/12	5	NM_001396050.1	P1
SCART1	ENST00000463137.5	n.2521C>G		non_coding_transcript_exon_variant	6/11	2
SCART1	ENST00000482993.6	n.2903C>G		non_coding_transcript_exon_variant	5/10	2
SCART1	ENST00000488261.6	n.2669C>G		non_coding_transcript_exon_variant	4/14	2

Frequencies

GnomAD3 genomes AF: 0.766 AC: 116464 AN: 151948 Hom.: 46895 Cov.: 35

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.799

GnomAD3 exomes AF: 0.834 AC: 15002 AN: 17986 Hom.: 6270 AF XY: 0.842 AC XY: 8263 AN XY: 9814

Gnomad AFR exome AF: 0.502

Gnomad AMR exome AF: 0.732

Gnomad ASJ exome AF: 0.889

Gnomad EAS exome AF: 0.748

Gnomad SAS exome AF: 0.901

Gnomad FIN exome AF: 0.899

Gnomad NFE exome AF: 0.880

Gnomad OTH exome AF: 0.836

GnomAD4 exome AF: 0.873 AC: 340553 AN: 390032 Hom.: 149320 Cov.: 0 AF XY: 0.878 AC XY: 181751 AN XY: 207108

Gnomad4 AFR exome AF: 0.498

Gnomad4 AMR exome AF: 0.752

Gnomad4 ASJ exome AF: 0.899

Gnomad4 EAS exome AF: 0.728

Gnomad4 SAS exome AF: 0.917

Gnomad4 FIN exome AF: 0.911

Gnomad4 NFE exome AF: 0.895

Gnomad4 OTH exome AF: 0.854

GnomAD4 genome AF: 0.766 AC: 116486 AN: 152058 Hom.: 46894 Cov.: 35 AF XY: 0.770 AC XY: 57206 AN XY: 74324

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.899

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.895

Gnomad4 OTH AF: 0.802

Alfa AF: 0.769 Hom.: 2930

TwinsUK AF: 0.900 AC: 3339

ALSPAC AF: 0.899 AC: 3466

ExAC AF: 0.797 AC: 63943

Asia WGS AF: 0.814 AC: 2817 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_noAF	Benign	-0.44
Cadd	Benign	21
Dann	Uncertain	1.0
Eigen	Benign	0.085
Eigen_PC	Benign	-0.037
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.1e-24	P
MutPred		0.60		Gain of helix (P = 0.0425);
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.20

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs731947; hg19: chr10-135273463; COSMIC: COSV62986107; COSMIC: COSV62986107;