11-57485169-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003627.6(SLC43A1):​c.1607G>A​(p.Arg536Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R536W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLC43A1
NM_003627.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0270
Variant links:
Genes affected
SLC43A1 (HGNC:9225): (solute carrier family 43 member 1) SLC43A1 belongs to the system L family of plasma membrane carrier proteins that transports large neutral amino acids (Babu et al., 2003 [PubMed 12930836]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04113689).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC43A1NM_003627.6 linkc.1607G>A p.Arg536Gln missense_variant Exon 15 of 15 ENST00000278426.8 NP_003618.1 O75387-1A0A024R4Y3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC43A1ENST00000278426.8 linkc.1607G>A p.Arg536Gln missense_variant Exon 15 of 15 1 NM_003627.6 ENSP00000278426.3 O75387-1
SLC43A1ENST00000528450.5 linkc.1607G>A p.Arg536Gln missense_variant Exon 15 of 15 1 ENSP00000435673.1 O75387-1

Frequencies

GnomAD3 genomes
AF:
0.0000921
AC:
14
AN:
152086
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251128
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000616
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000127
AC:
185
AN:
1461832
Hom.:
0
Cov.:
30
AF XY:
0.000120
AC XY:
87
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000163
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000920
AC:
14
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000672
AC XY:
5
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000981
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1607G>A (p.R536Q) alteration is located in exon 15 (coding exon 14) of the SLC43A1 gene. This alteration results from a G to A substitution at nucleotide position 1607, causing the arginine (R) at amino acid position 536 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.60
.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.041
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Benign
0.25
T
PROVEAN
Benign
-0.70
N;N
REVEL
Benign
0.031
Sift
Benign
0.56
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.019
B;B
Vest4
0.077
MVP
0.54
MPC
0.30
ClinPred
0.044
T
GERP RS
0.73
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.060
gMVP
0.11

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs376876605; hg19: chr11-57252642; API