17-1575633-C-A

Variant names:

• chr17-1575633-C-A
• rs947286216
• NM_152346.3:c.1681G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152346.3(SLC43A2):​c.1681G>T​(p.Gly561Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G561S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36896226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3	c.1681G>T	p.Gly561Cys	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.1681G>T	p.Gly561Cys	missense_variant	Exon 14 of 14	1	NM_152346.3	ENSP00000301335.5
SLC43A2	ENST00000571650.5	c.1693G>T	p.Gly565Cys	missense_variant	Exon 15 of 15	1		ENSP00000461382.1
SLC43A2	ENST00000412517.3	c.1270G>T	p.Gly424Cys	missense_variant	Exon 10 of 10	2		ENSP00000408284.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N;.;N
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.40
MutPred		0.36		Loss of disorder (P = 0.053);.;.;
MVP		0.53
MPC		1.2
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.37
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs947286216; hg19: chr17-1478927;