rs137987228

Variant names:

• chr17-1585932-C-T
• rs137987228
• NM_152346.3:c.1198G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-1585932-C-T
• chr17-1585932-C-G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_152346.3(SLC43A2):​c.1198G>A​(p.Glu400Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000184 in 1,613,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: SLC43A2 NM_152346.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.45
• Publications: 3 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.331577).

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.1198G>A	p.Glu400Lys	missense	Exon 10 of 14	NP_689559.1	Q8N370-1
	SLC43A2	NM_001284498.2		c.1210G>A	p.Glu404Lys	missense	Exon 11 of 15	NP_001271427.1	Q8N370-3
	SLC43A2	NM_001321364.2		c.1210G>A	p.Glu404Lys	missense	Exon 11 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.1198G>A	p.Glu400Lys	missense	Exon 10 of 14	ENSP00000301335.5	Q8N370-1
	SLC43A2	ENST00000571650.5	TSL:1	c.1210G>A	p.Glu404Lys	missense	Exon 11 of 15	ENSP00000461382.1	Q8N370-3
	SLC43A2	ENST00000572135.5	TSL:1	n.1381G>A		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000640 AC: 16 AN: 250010 AF XY: 0.0000517

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000977

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000194 AC: 284 AN: 1461372 Hom.: 0 Cov.: 34 AF XY: 0.000154 AC XY: 112 AN XY: 726978

African (AFR) AF: 0.000269 AC: 9 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.000234 AC: 260 AN: 1111988

Other (OTH) AF: 0.000132 AC: 8 AN: 60388

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152226 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74366

African (AFR) AF: 0.0000241 AC: 1 AN: 41466

American (AMR) AF: 0.000262 AC: 4 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.000128

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.000273

EpiControl AF: 0.000119

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	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.14
Sift	Benign	0.51	T
Sift4G	Benign	0.87	T
Polyphen		0.0020	B
Vest4		0.56
MVP		0.43
MPC		0.44
ClinPred		0.039	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.27
Mutation Taster		=85/15	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: rs137987228; hg19: chr17-1489226; COSMIC: COSV104398518; COSMIC: COSV104398518;