17-1575695-C-T

Variant names:

• chr17-1575695-C-T
• rs201032490
• NM_152346.3:c.1619G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152346.3(SLC43A2):​c.1619G>A​(p.Arg540His) variant causes a missense change. The variant allele was found at a frequency of 0.000214 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (0 hom.)
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19090134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3	c.1619G>A	p.Arg540His	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.1619G>A	p.Arg540His	missense_variant	Exon 14 of 14	1	NM_152346.3	ENSP00000301335.5
SLC43A2	ENST00000571650.5	c.1631G>A	p.Arg544His	missense_variant	Exon 15 of 15	1		ENSP00000461382.1
SLC43A2	ENST00000412517.3	c.1208G>A	p.Arg403His	missense_variant	Exon 10 of 10	2		ENSP00000408284.3

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000185 AC: 46 AN: 248020 Hom.: 0 AF XY: 0.000223 AC XY: 30 AN XY: 134650

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000465

Gnomad NFE exome AF: 0.000370

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000224 AC: 328 AN: 1461712 Hom.: 0 Cov.: 31 AF XY: 0.000223 AC XY: 162 AN XY: 727164

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.000264

Gnomad4 OTH exome AF: 0.000348

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74482

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000133 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000321 AC: 39

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1619G>A (p.R540H) alteration is located in exon 14 (coding exon 13) of the SLC43A2 gene. This alteration results from a G to A substitution at nucleotide position 1619, causing the arginine (R) at amino acid position 540 to be replaced by a histidine (H). 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	Benign	0.084
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.37	T;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N;.;N
REVEL	Uncertain	0.52
Sift	Benign	0.11	T;.;T
Sift4G	Benign	0.096	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.21
MVP		0.87
MPC		0.48
ClinPred		0.13	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.29
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201032490; hg19: chr17-1478989;