Genetic Variant SLC10A3:p.Ala412Thr (chrX-154487707-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_019848.5(SLC10A3):c.1234G>A(p.Ala412Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000888 in 112,671 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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., 0 hem., cov: 24)

Consequence

SLC10A3
NM_019848.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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]

SLC10A3 links:

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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=0.17082074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC10A3	NM_019848.5 link	c.1234G>A	p.Ala412Thr	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
SLC10A3	ENST00000651600.1 link	c.1234G>A	p.Ala412Thr	missense_variant	Exon 2 of 2		NM_019848.5	ENSP00000499188.1		P09131-1

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112671

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34821

show subpopulations

Gnomad AFR

AF:

0.0000322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112671

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34821

show subpopulations

Gnomad4 AFR

AF:

0.0000322

Gnomad4 AMR

AF:

0.00

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1234G>A (p.A412T) 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 1234, causing the alanine (A) at amino acid position 412 to be replaced by a threonine (T). 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

0.085

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

.;T;.;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;T;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.86

.;L;.;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.95

N;N;N;N

REVEL

Benign

0.074

Sift

Benign

0.13

T;D;T;D

Sift4G

Uncertain

0.059

T;T;T;T

Polyphen

0.87

.;P;.;P

Vest4

0.19

MutPred

0.32

.;Gain of methylation at K408 (P = 0.0559);.;Gain of methylation at K408 (P = 0.0559);

MVP

0.21

MPC

0.47

ClinPred

0.72

GERP RS

2.7

Varity_R

0.096

gMVP

0.58

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over