Variant 13-28712712-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_181785.4(SLC46A3):c.1028C>T(p.Ala343Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000624 in 1,603,046 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 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

SLC46A3
NM_181785.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.79

Variant links:

Genes affected

SLC46A3 (HGNC:27501): (solute carrier family 46 member 3) The protein encoded by this gene is a member of a transmembrane protein family that transports small molecules across membranes. The encoded protein has been found in lysosomal membranes, where it can transport catabolites from the lysosomes to the cytoplasm. This protein has been shown to be an effective transporter of the cytotoxic drug maytansine, which is used in antibody-based targeting of cancer cells. [provided by RefSeq, Dec 2016]

SLC46A3 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=0.07338622).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC46A3	NM_181785.4 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/6	ENST00000266943.11	NP_861450.1	Q7Z3Q1-1A0A024RDN9
SLC46A3	NM_001135919.2 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/7		NP_001129391.1	Q7Z3Q1-2
SLC46A3	NM_001347960.2 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/6		NP_001334889.1	Q7Z3Q1-1A0A024RDN9
SLC46A3	XM_005266361.3 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/7		XP_005266418.1	Q7Z3Q1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC46A3	ENST00000266943.11 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/6	1	NM_181785.4	ENSP00000266943.7		Q7Z3Q1-1
SLC46A3	ENST00000380814.4 linkuse as main transcript	c.1028C>T	p.Ala343Val	missense_variant	3/7	1		ENSP00000370192.4		Q7Z3Q1-2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

240732

Hom.:

AF XY:

0.0000768

AC XY:

AN XY:

130142

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.0000944

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:

0.00

GnomAD4 exome

AF:

0.0000317

AC:

AN:

1450938

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

721646

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.0000481

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

AF:

0.000355

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.0000655

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:

0.0000826

Hom.:

Bravo

AF:

0.000389

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.1028C>T (p.A343V) alteration is located in exon 3 (coding exon 2) of the SLC46A3 gene. This alteration results from a C to T substitution at nucleotide position 1028, causing the alanine (A) at amino acid position 343 to be replaced by a valine (V). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.80

P;P

Vest4

0.35

MVP

0.36

MPC

0.22

ClinPred

0.083

GERP RS

4.5

Varity_R

0.30

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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