X-154488194-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_019848.5(SLC10A3):​c.747G>A​(p.Met249Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,210,084 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 0.000015 ( 0 hom. 3 hem. )

Consequence

SLC10A3
NM_019848.5 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0510
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06256598).
BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC10A3NM_019848.5 linkc.747G>A p.Met249Ile 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.747G>A p.Met249Ile missense_variant Exon 2 of 2 NM_019848.5 ENSP00000499188.1 P09131-1

Frequencies

GnomAD3 genomes
AF:
0.00000890
AC:
1
AN:
112420
Hom.:
0
Cov.:
24
AF XY:
0.0000289
AC XY:
1
AN XY:
34580
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000934
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000874
AC:
16
AN:
183146
Hom.:
0
AF XY:
0.0000442
AC XY:
3
AN XY:
67840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000547
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:
0.00
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000155
AC:
17
AN:
1097664
Hom.:
0
Cov.:
31
AF XY:
0.00000826
AC XY:
3
AN XY:
363310
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000483
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000890
AC:
1
AN:
112420
Hom.:
0
Cov.:
24
AF XY:
0.0000289
AC XY:
1
AN XY:
34580
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000934
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453
ExAC
AF:
0.0000988
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.747G>A (p.M249I) 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 747, causing the methionine (M) at amino acid position 249 to be replaced by an isoleucine (I). 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
0.28
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.041
.;T;.;T
FATHMM_MKL
Benign
0.58
D
LIST_S2
Benign
0.83
T;T;T;.
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.063
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-0.90
.;N;.;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.89
N;N;N;N
REVEL
Benign
0.042
Sift
Benign
0.20
T;T;T;T
Sift4G
Benign
0.19
T;T;T;T
Polyphen
0.075
.;B;.;B
Vest4
0.30
MutPred
0.40
.;Gain of catalytic residue at L254 (P = 0.02);.;Gain of catalytic residue at L254 (P = 0.02);
MVP
0.068
MPC
0.61
ClinPred
0.060
T
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.33
gMVP
0.45

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: rs782584318; hg19: chrX-153716533; API