rs35790011

Variant names:

• chr17-19560278-G-A
• rs35790011
• NM_018242.3:c.1012G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-19560278-G-A
• chr17-19560278-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018242.3(SLC47A1):​c.1012G>A​(p.Val338Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,613,676 control chromosomes in the GnomAD database, including 155 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.017 (81 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (74 hom.)
• Consequence: SLC47A1 NM_018242.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• Publications: 17 publications found

Genes affected

SLC47A1 (HGNC:25588): (solute carrier family 47 member 1) This gene is located within the Smith-Magenis syndrome region on chromosome 17. It encodes a protein of unknown function. [provided by RefSeq, Jul 2008]

ENSG00000262769 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003266096).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC47A1	NM_018242.3	c.1012G>A	p.Val338Ile	missense_variant	Exon 11 of 17	ENST00000270570.8	NP_060712.2
LOC105371578	XR_934310.4	n.*17C>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC47A1	ENST00000270570.8	c.1012G>A	p.Val338Ile	missense_variant	Exon 11 of 17	1	NM_018242.3	ENSP00000270570.4

Frequencies

GnomAD3 genomes AF: 0.0173 AC: 2636 AN: 152090 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00454 AC: 1138 AN: 250696 AF XY: 0.00323

Gnomad AFR exome AF: 0.0624

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00184 AC: 2689 AN: 1461468 Hom.: 74 Cov.: 30 AF XY: 0.00155 AC XY: 1129 AN XY: 727026

African (AFR) AF: 0.0644 AC: 2155 AN: 33470

American (AMR) AF: 0.00282 AC: 126 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39694

South Asian (SAS) AF: 0.000371 AC: 32 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5734

European-Non Finnish (NFE) AF: 0.0000720 AC: 80 AN: 1111776

Other (OTH) AF: 0.00460 AC: 278 AN: 60374

GnomAD4 genome AF: 0.0174 AC: 2641 AN: 152208 Hom.: 81 Cov.: 32 AF XY: 0.0168 AC XY: 1247 AN XY: 74420

African (AFR) AF: 0.0599 AC: 2488 AN: 41510

American (AMR) AF: 0.00693 AC: 106 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68012

Other (OTH) AF: 0.0118 AC: 25 AN: 2110

Alfa AF: 0.00479 Hom.: 35

Bravo AF: 0.0190

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0576 AC: 254

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00582 AC: 707

Asia WGS AF: 0.00404 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0069	.;T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.74	T;T;T;T
MetaRNN	Benign	0.0033	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;.;L;L
PhyloP100		0.25
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.71	.;N;N;N
REVEL	Benign	0.021
Sift	Benign	0.12	.;T;T;T
Sift4G	Benign	0.093	T;T;T;T
Polyphen		0.048, 0.11, 0.042	.;B;B;B
Vest4		0.090
MVP		0.26
MPC		0.22
ClinPred		0.0015	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.095
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs35790011; hg19: chr17-19463591; COSMIC: COSV54499011; COSMIC: COSV54499011;