chr17-1585946-G-C

Variant names:

• chr17-1585946-G-C
• rs529170281
• NM_152346.3:c.1184C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152346.3(SLC43A2):​c.1184C>G​(p.Ala395Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. A395D) 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: 0.347
• Publications: 1 publications found

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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03588566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3	c.1184C>G	p.Ala395Gly	missense_variant	Exon 10 of 14	ENST00000301335.10	NP_689559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC43A2	ENST00000301335.10	c.1184C>G	p.Ala395Gly	missense_variant	Exon 10 of 14	1	NM_152346.3	ENSP00000301335.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.6
DANN	Benign	0.56
DEOGEN2	Benign	0.24	T;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.080	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.81	N;.;.
PhyloP100		0.35
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.93	N;.;N
REVEL	Benign	0.066
Sift	Benign	0.40	T;.;T
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.26		Gain of helix (P = 0.0854);.;.;
MVP		0.040
MPC		0.39
ClinPred		0.11	T
GERP RS		-4.8
Varity_R		0.045
gMVP		0.12

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

Other links and lift over

dbSNP: rs529170281; hg19: chr17-1489240;