17-1575633-C-G

Variant names:

• chr17-1575633-C-G
• rs947286216
• NM_152346.3:c.1681G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152346.3(SLC43A2):​c.1681G>C​(p.Gly561Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000821 in 1,461,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. G561S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3135542).

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.1681G>C	p.Gly561Arg	missense	Exon 14 of 14	NP_689559.1	Q8N370-1
	SLC43A2	NM_001284498.2		c.1693G>C	p.Gly565Arg	missense	Exon 15 of 15	NP_001271427.1	Q8N370-3
	SLC43A2	NM_001321364.2		c.1693G>C	p.Gly565Arg	missense	Exon 15 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.1681G>C	p.Gly561Arg	missense	Exon 14 of 14	ENSP00000301335.5	Q8N370-1
	SLC43A2	ENST00000571650.5	TSL:1	c.1693G>C	p.Gly565Arg	missense	Exon 15 of 15	ENSP00000461382.1	Q8N370-3
	SLC43A2	ENST00000952273.1		c.1762G>C	p.Gly588Arg	missense	Exon 16 of 16	ENSP00000622332.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1461824 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.34
MutPred		0.33		Gain of solvent accessibility (P = 0.0171)
MVP		0.51
MPC		1.2
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.22
gMVP		0.65
Mutation Taster		=74/26	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: rs947286216; hg19: chr17-1478927;