17-1585920-C-G

Variant names:

• chr17-1585920-C-G
• rs143568503
• NM_152346.3:c.1210G>C

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.1210G>C​(p.Ala404Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,390 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A404T) 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: -0.964
• Publications: 0 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=0.04684621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC43A2	NM_152346.3	c.1210G>C	p.Ala404Pro	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.1210G>C	p.Ala404Pro	missense_variant	Exon 10 of 14	1	NM_152346.3	ENSP00000301335.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461390 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111970

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.27
DANN	Benign	0.92
DEOGEN2	Benign	0.23	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.66	N;.;.
PhyloP100		-0.96
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.89	N;.;N
REVEL	Benign	0.0040
Sift	Benign	0.23	T;.;T
Sift4G	Benign	0.32	T;T;T
Polyphen		0.28	B;B;.
Vest4		0.22
MutPred		0.34		Gain of methylation at K402 (P = 0.0641);.;.;
MVP		0.17
MPC		0.56
ClinPred		0.032	T
GERP RS		-2.6
Varity_R		0.073
gMVP		0.31
Mutation Taster		=88/12	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

Other links and lift over

dbSNP: rs143568503; hg19: chr17-1489214;