rs759744869

Variant names:

• chr17-1575759-C-G
• rs759744869
• NM_152346.3:c.1555G>C

Your query was ambiguous. Multiple possible variants found:

• chr17-1575759-C-G
• chr17-1575759-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

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]

ACMG classification

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	c.1555G>C	p.Val519Leu	missense_variant	Exon 14 of 14	ENST00000301335.10	NP_689559.1

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1458378 Hom.: 0 Cov.: 31 AF XY: 0.00000414 AC XY: 3 AN XY: 725212

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 86008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52892

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4978

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110702

Other (OTH) AF: 0.00 AC: 0 AN: 60170

GnomAD4 genome Cov.: 33

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	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.1	L;.;.
PhyloP100		1.4
PrimateAI	Uncertain	0.54	T
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	D
GERP RS		3.7
Varity_R		0.12
gMVP		0.54
Mutation Taster		=73/27	polymorphism

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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Other links and lift over

dbSNP: rs759744869; hg19: chr17-1479053;