Genetic Variant SLC43A2:p.Asp513Gly (chr17-1576607-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152346.3(SLC43A2):c.1538A>G(p.Asp513Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC43A2
NM_152346.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.914

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3 link	c.1538A>G	p.Asp513Gly	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.1538A>G	p.Asp513Gly	missense_variant	Exon 13 of 14	1	NM_152346.3	ENSP00000301335.5	Q8N370-1
SLC43A2	ENST00000571650.5 link	c.1550A>G	p.Asp517Gly	missense_variant	Exon 14 of 15	1		ENSP00000461382.1	Q8N370-3
SLC43A2	ENST00000412517.3 link	c.1127A>G	p.Asp376Gly	missense_variant	Exon 9 of 10	2		ENSP00000408284.3	Q8N370-4
SLC43A2	ENST00000576537.1 link	n.570A>G		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454044

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723492

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33378

American (AMR)

AF:

0.00

AC:

AN:

44188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39640

South Asian (SAS)

AF:

0.00

AC:

AN:

86144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47456

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111134

Other (OTH)

AF:

0.00

AC:

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1538A>G (p.D513G) alteration is located in exon 13 (coding exon 12) of the SLC43A2 gene. This alteration results from a A to G substitution at nucleotide position 1538, causing the aspartic acid (D) at amino acid position 513 to be replaced by a glycine (G). 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

Pathogenic

0.82

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

T;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.082

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.45

MutationAssessor

Pathogenic

3.2

M;.;.

PhyloP100

7.7

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-4.9

D;.;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0040

D;.;D

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.94

MutPred

0.75

Loss of stability (P = 0.0522);.;.;

MVP

0.64

MPC

1.1

ClinPred

1.0

GERP RS

5.8

Varity_R

0.73

gMVP

0.86

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over