Genetic Variant SLC43A2:p.Met506Leu (chr17-1576629-T-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152346.3(SLC43A2):c.1516A>C(p.Met506Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,458,070 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: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

SLC43A2
NM_152346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26921147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3 link	c.1516A>C	p.Met506Leu	missense_variant	Exon 13 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.1516A>C	p.Met506Leu	missense_variant	Exon 13 of 14	1	NM_152346.3	ENSP00000301335.5	Q8N370-1
SLC43A2	ENST00000571650.5 link	c.1528A>C	p.Met510Leu	missense_variant	Exon 14 of 15	1		ENSP00000461382.1	Q8N370-3
SLC43A2	ENST00000412517.3 link	c.1105A>C	p.Met369Leu	missense_variant	Exon 9 of 10	2		ENSP00000408284.3	Q8N370-4
SLC43A2	ENST00000576537.1 link	n.548A>C		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1458070

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1111918

Other (OTH)

AF:

0.00

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1516A>C (p.M506L) alteration is located in exon 13 (coding exon 12) of the SLC43A2 gene. This alteration results from a A to C substitution at nucleotide position 1516, causing the methionine (M) at amino acid position 506 to be replaced by a leucine (L). 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

0.23

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.27

T;.;.

Eigen

Benign

-0.050

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.023

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.2

M;.;.

PhyloP100

4.9

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.6

N;.;N

REVEL

Benign

0.21

Sift

Benign

0.052

T;.;T

Sift4G

Benign

0.092

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.37

MutPred

0.47

Gain of glycosylation at P501 (P = 0.3135);.;.;

MVP

0.77

MPC

0.37

ClinPred

0.91

GERP RS

5.8

Varity_R

0.32

gMVP

0.60

Mutation Taster

=74/26

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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chr17-1576629-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over