rs731947

Variant names:

• chr10-133459959-C-G
• rs731947
• NM_001396050.1:c.1758C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-133459959-C-G
• chr10-133459959-C-T

Variant summary

Our verdict is Benign. The variant received -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. 7/11 in silico tools predict 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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001396050.1. 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
	SCART1	NM_001396050.1	MANE Select	c.1758C>G	p.Asp586Glu	missense	Exon 6 of 12	NP_001382979.1	Q4G0T1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCART1	ENST00000640237.2	TSL:5 MANE Select	c.1758C>G	p.Asp586Glu	missense	Exon 6 of 12	ENSP00000491516.1	Q4G0T1-1
	SCART1	ENST00000463137.5	TSL:2	n.2521C>G		non_coding_transcript_exon	Exon 6 of 11
	SCART1	ENST00000482993.6	TSL:2	n.2903C>G		non_coding_transcript_exon	Exon 5 of 10

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

GnomAD2 exomes AF: 0.834 AC: 15002 AN: 17986 AF XY: 0.842

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 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

African (AFR) AF: 0.498 AC: 4041 AN: 8108

American (AMR) AF: 0.752 AC: 7936 AN: 10556

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 10697 AN: 11894

East Asian (EAS) AF: 0.728 AC: 17980 AN: 24704

South Asian (SAS) AF: 0.917 AC: 32976 AN: 35960

European-Finnish (FIN) AF: 0.911 AC: 26868 AN: 29490

Middle Eastern (MID) AF: 0.906 AC: 2052 AN: 2266

European-Non Finnish (NFE) AF: 0.895 AC: 218106 AN: 243768

Other (OTH) AF: 0.854 AC: 19897 AN: 23286

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

African (AFR) AF: 0.485 AC: 20099 AN: 41452

American (AMR) AF: 0.764 AC: 11688 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3472

East Asian (EAS) AF: 0.742 AC: 3814 AN: 5140

South Asian (SAS) AF: 0.908 AC: 4386 AN: 4828

European-Finnish (FIN) AF: 0.925 AC: 9823 AN: 10614

Middle Eastern (MID) AF: 0.914 AC: 267 AN: 292

European-Non Finnish (NFE) AF: 0.895 AC: 60824 AN: 67944

Other (OTH) AF: 0.802 AC: 1695 AN: 2114

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 v4.9

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
PhyloP100		0.30
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
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

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