17-1590850-C-T

Variant names:

• chr17-1590850-C-T
• rs962359625
• NM_152346.3:c.1030G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152346.3(SLC43A2):​c.1030G>A​(p.Ala344Thr) 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.836

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152346.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC43A2	NM_152346.3	MANE Select	c.1030G>A	p.Ala344Thr	missense	Exon 9 of 14	NP_689559.1	Q8N370-1
	SLC43A2	NM_001284498.2		c.1030G>A	p.Ala344Thr	missense	Exon 9 of 15	NP_001271427.1	Q8N370-3
	SLC43A2	NM_001321364.2		c.1030G>A	p.Ala344Thr	missense	Exon 9 of 15	NP_001308293.1	Q8N370-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC43A2	ENST00000301335.10	TSL:1 MANE Select	c.1030G>A	p.Ala344Thr	missense	Exon 9 of 14	ENSP00000301335.5	Q8N370-1
	SLC43A2	ENST00000571650.5	TSL:1	c.1030G>A	p.Ala344Thr	missense	Exon 9 of 15	ENSP00000461382.1	Q8N370-3
	SLC43A2	ENST00000572135.5	TSL:1	n.1213G>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1403750 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 692560

African (AFR) AF: 0.00 AC: 0 AN: 32306

American (AMR) AF: 0.00 AC: 0 AN: 35734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 36998

South Asian (SAS) AF: 0.00 AC: 0 AN: 79552

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080950

Other (OTH) AF: 0.00 AC: 0 AN: 58184

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.4	L
PhyloP100		7.6
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.1	N
REVEL	Pathogenic	0.68
Sift	Benign	0.23	T
Sift4G	Benign	0.12	T
Polyphen		0.85	P
Vest4		0.84
MutPred		0.61		Loss of helix (P = 0.1706)
MVP		0.81
MPC		1.2
ClinPred		0.90	D
GERP RS		5.7
Varity_R		0.17
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs962359625; hg19: chr17-1494144;