rs35790011

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.017 ( 81 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 74 hom. )

Consequence

SLC47A1
NM_018242.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.246
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons MANE UniProt
SLC47A1NM_018242.3 linkuse as main transcriptc.1012G>A p.Val338Ile missense_variant 11/17 ENST00000270570.8
LOC105371578XR_934310.4 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC47A1ENST00000270570.8 linkuse as main transcriptc.1012G>A p.Val338Ile missense_variant 11/171 NM_018242.3 P1Q96FL8-1
ENST00000574267.1 linkuse as main transcriptn.563C>T non_coding_transcript_exon_variant 4/45

Frequencies

GnomAD3 genomes
AF:
0.0173
AC:
2636
AN:
152090
Hom.:
80
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00454
AC:
1138
AN:
250696
Hom.:
34
AF XY:
0.00323
AC XY:
437
AN XY:
135460
show subpopulations
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 SAS exome
AF:
0.000327
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0644
Gnomad4 AMR exome
AF:
0.00282
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000371
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000720
Gnomad4 OTH exome
AF:
0.00460
GnomAD4 genome
AF:
0.0174
AC:
2641
AN:
152208
Hom.:
81
Cov.:
32
AF XY:
0.0168
AC XY:
1247
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0599
Gnomad4 AMR
AF:
0.00693
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000623
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00381
Hom.:
25
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
MutationTaster
Benign
1.0
N;N;N;N;N;N
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35790011; hg19: chr17-19463591; COSMIC: COSV54499011; COSMIC: COSV54499011; API