Genetic Variant NM_003627.6:c.1498G>A (chr11-57487130-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_003627.6(SLC43A1):c.1498G>A(p.Ala500Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLC43A1
NM_003627.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.227

Variant links:

Genes affected

SLC43A1 (HGNC:9225): (solute carrier family 43 member 1) SLC43A1 belongs to the system L family of plasma membrane carrier proteins that transports large neutral amino acids (Babu et al., 2003 [PubMed 12930836]).[supplied by OMIM, Mar 2008]

SLC43A1 links:

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=0.14352009).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A1	NM_003627.6 link	c.1498G>A	p.Ala500Thr	missense_variant	Exon 14 of 15	ENST00000278426.8	NP_003618.1	O75387-1A0A024R4Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC43A1	ENST00000278426.8 link	c.1498G>A	p.Ala500Thr	missense_variant	Exon 14 of 15	1	NM_003627.6	ENSP00000278426.3	O75387-1
SLC43A1	ENST00000528450.5 link	c.1498G>A	p.Ala500Thr	missense_variant	Exon 14 of 15	1		ENSP00000435673.1	O75387-1
SLC43A1	ENST00000525764.5 link	c.*50G>A		downstream_gene_variant		3		ENSP00000435803.1	H0YEH0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251332

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1498G>A (p.A500T) alteration is located in exon 14 (coding exon 13) of the SLC43A1 gene. This alteration results from a G to A substitution at nucleotide position 1498, causing the alanine (A) at amino acid position 500 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

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.30

T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.085

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.037

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.068

Sift

Benign

0.19

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.0030

B;B

Vest4

0.37

MutPred

0.49

Loss of stability (P = 0.0234);Loss of stability (P = 0.0234);

MVP

0.53

MPC

0.26

ClinPred

0.14

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.092

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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