X-154487989-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019848.5(SLC10A3):​c.952G>A​(p.Val318Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,209,702 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 24)
Exomes 𝑓: 0.000050 ( 0 hom. 28 hem. )

Consequence

SLC10A3
NM_019848.5 missense

Scores

1
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.59
Variant links:
Genes affected
SLC10A3 (HGNC:22979): (solute carrier family 10 member 3) This gene maps to a GC-rich region of the X chromosome and was identified by its proximity to a CpG island. It is thought to be a housekeeping gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17109829).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A3NM_019848.5 linkc.952G>A p.Val318Met missense_variant Exon 2 of 2 ENST00000651600.1 NP_062822.1 P09131-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC10A3ENST00000651600.1 linkc.952G>A p.Val318Met missense_variant Exon 2 of 2 NM_019848.5 ENSP00000499188.1 P09131-1

Frequencies

GnomAD3 genomes
AF:
0.0000447
AC:
5
AN:
111915
Hom.:
0
Cov.:
24
AF XY:
0.0000587
AC XY:
2
AN XY:
34089
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000754
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000565
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000382
AC:
7
AN:
183110
Hom.:
0
AF XY:
0.0000590
AC XY:
4
AN XY:
67848
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000722
Gnomad SAS exome
AF:
0.000105
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000367
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000501
AC:
55
AN:
1097732
Hom.:
0
Cov.:
31
AF XY:
0.0000771
AC XY:
28
AN XY:
363360
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.000148
Gnomad4 FIN exome
AF:
0.0000250
Gnomad4 NFE exome
AF:
0.0000523
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000447
AC:
5
AN:
111970
Hom.:
0
Cov.:
24
AF XY:
0.0000586
AC XY:
2
AN XY:
34154
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000756
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000565
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
1
Bravo
AF:
0.0000718
ExAC
AF:
0.0000577
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.952G>A (p.V318M) alteration is located in exon 2 (coding exon 1) of the SLC10A3 gene. This alteration results from a G to A substitution at nucleotide position 952, causing the valine (V) at amino acid position 318 to be replaced by a methionine (M). 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
0.27
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.091
.;T;.;T
FATHMM_MKL
Benign
0.74
D
LIST_S2
Uncertain
0.91
D;D;D;.
M_CAP
Pathogenic
0.29
D
MetaRNN
Benign
0.17
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
.;M;.;M
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Benign
0.16
Sift
Uncertain
0.028
D;D;D;D
Sift4G
Benign
0.068
T;T;T;T
Polyphen
0.94
.;P;.;P
Vest4
0.23
MutPred
0.51
.;Gain of helix (P = 0.0425);.;Gain of helix (P = 0.0425);
MVP
0.39
MPC
0.94
ClinPred
0.18
T
GERP RS
3.3
Varity_R
0.22
gMVP
0.83

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: rs782319797; hg19: chrX-153716328; COSMIC: COSV99682173; COSMIC: COSV99682173; API