Genetic Variant NM_152346.3:c.1555G>C (chr17-1575759-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152346.3(SLC43A2):c.1555G>C(p.Val519Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V519M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC43A2
NM_152346.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.42

Publications

0 publications found

Variant links:

Genes affected

SLC43A2 (HGNC:23087): (solute carrier family 43 member 2) This gene encodes a member of the L-amino acid transporter-3 or SLC43 family of transporters. The encoded protein mediates sodium-, chloride-, and pH-independent transport of L-isomers of neutral amino acids, including leucine, phenylalanine, valine and methionine. This protein may contribute to the transfer of amino acids across the placental membrane to the fetus. [provided by RefSeq, Mar 2016]

SLC43A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25124997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3 link	c.1555G>C	p.Val519Leu	missense_variant	Exon 14 of 14	ENST00000301335.10	NP_689559.1	Q8N370-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC43A2	ENST00000301335.10 link	c.1555G>C	p.Val519Leu	missense_variant	Exon 14 of 14	1	NM_152346.3	ENSP00000301335.5	Q8N370-1
SLC43A2	ENST00000571650.5 link	c.1567G>C	p.Val523Leu	missense_variant	Exon 15 of 15	1		ENSP00000461382.1	Q8N370-3
SLC43A2	ENST00000412517.3 link	c.1144G>C	p.Val382Leu	missense_variant	Exon 10 of 10	2		ENSP00000408284.3	Q8N370-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458378

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.00

AC:

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26052

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000233

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52892

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4978

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1110702

Other (OTH)

AF:

0.00

AC:

AN:

60170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.23

T;.;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.87

M_CAP

Benign

0.040

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.1

L;.;.

PhyloP100

1.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.19

N;.;N

REVEL

Uncertain

0.36

Sift

Benign

0.63

T;.;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.010

B;B;.

Vest4

0.38

MutPred

0.26

Loss of sheet (P = 0.0181);.;.;

MVP

0.80

MPC

0.39

ClinPred

0.65

GERP RS

3.7

Varity_R

0.12

gMVP

0.54

Mutation Taster

=73/27

polymorphism

(source)

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

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NM_152346.3:c.1555G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over