5-151467783-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_078483.4(SLC36A1):​c.581C>T​(p.Ser194Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SLC36A1
NM_078483.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70
Variant links:
Genes affected
SLC36A1 (HGNC:18761): (solute carrier family 36 member 1) This gene encodes a member of the eukaryote-specific amino acid/auxin permease (AAAP) 1 transporter family. The encoded protein functions as a proton-dependent, small amino acid transporter. This gene is clustered with related family members on chromosome 5q33.1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1596545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC36A1NM_078483.4 linkc.581C>T p.Ser194Leu missense_variant Exon 7 of 11 ENST00000243389.8 NP_510968.2 Q7Z2H8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC36A1ENST00000243389.8 linkc.581C>T p.Ser194Leu missense_variant Exon 7 of 11 1 NM_078483.4 ENSP00000243389.3 Q7Z2H8-1
SLC36A1ENST00000521925.5 linkc.581C>T p.Ser194Leu missense_variant Exon 7 of 10 1 ENSP00000430305.1 E7EW39
SLC36A1ENST00000429484.6 linkc.581C>T p.Ser194Leu missense_variant Exon 7 of 9 1 ENSP00000395640.2 Q7Z2H8-4
SLC36A1ENST00000520701.5 linkc.581C>T p.Ser194Leu missense_variant Exon 7 of 11 5 ENSP00000428140.1 Q7Z2H8-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152052
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000775
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000676
AC:
17
AN:
251488
Hom.:
0
AF XY:
0.0000736
AC XY:
10
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000924
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461868
Hom.:
0
Cov.:
32
AF XY:
0.0000206
AC XY:
15
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000378
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152170
Hom.:
0
Cov.:
30
AF XY:
0.0000672
AC XY:
5
AN XY:
74404
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000777
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000659
AC:
8

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.581C>T (p.S194L) alteration is located in exon 7 (coding exon 6) of the SLC36A1 gene. This alteration results from a C to T substitution at nucleotide position 581, causing the serine (S) at amino acid position 194 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.045
T;.;T;.;.
Eigen
Benign
-0.082
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
.;D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
1.1
L;L;L;L;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Benign
-0.070
N;N;N;.;N
REVEL
Benign
0.25
Sift
Benign
0.59
T;T;T;.;T
Sift4G
Benign
0.35
T;T;T;T;T
Polyphen
0.46
P;.;P;.;B
Vest4
0.83
MutPred
0.54
Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);Loss of catalytic residue at S194 (P = 0.096);
MVP
0.32
MPC
0.37
ClinPred
0.099
T
GERP RS
4.8
Varity_R
0.17
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs571362914; hg19: chr5-150847344; API