NM_152346.3:c.1408G>C

Variant names:

• chr17-1578266-C-G
• NM_152346.3:c.1408G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152346.3(SLC43A2):​c.1408G>C​(p.Gly470Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3	c.1408G>C	p.Gly470Arg	missense_variant	Exon 12 of 14	ENST00000301335.10	NP_689559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC43A2	ENST00000301335.10	c.1408G>C	p.Gly470Arg	missense_variant	Exon 12 of 14	1	NM_152346.3	ENSP00000301335.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1408G>C (p.G470R) alteration is located in exon 12 (coding exon 11) of the SLC43A2 gene. This alteration results from a G to C substitution at nucleotide position 1408, causing the glycine (G) at amino acid position 470 to be replaced by an arginine (R). 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	1.0
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D;.;.
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	3.1	M;.;.
PhyloP100		7.9
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.2	D;.;D
REVEL	Pathogenic	0.79
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.98
MutPred		0.74		Gain of methylation at G470 (P = 0.0092);.;.;
MVP		0.84
MPC		1.3
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.83
gMVP		0.97

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

hg19: chr17-1481560;