rs1143672

Variant names:

• chr3-121929321-G-A
• rs1143672
• NM_021082.4:c.1526G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-121929321-G-A
• chr3-121929321-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021082.4(SLC15A2):​c.1526G>A​(p.Arg509Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 1,612,066 control chromosomes in the GnomAD database, including 171,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (15684 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155488 hom.)
• Consequence: SLC15A2 NM_021082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 54 publications found

Genes affected

SLC15A2 (HGNC:10921): (solute carrier family 15 member 2) The mammalian kidney expresses a proton-coupled peptide transporter that is responsible for the absorption of small peptides, as well as beta-lactam antibiotics and other peptide-like drugs, from the tubular filtrate. This transporter, SLC15A2, belongs to the same gene family as SLC15A1 (MIM 600544), the proton-coupled peptide transporter found in the small intestine (Liu et al, 1995 [PubMed 7756356]).[supplied by OMIM, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3310764E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021082.4. 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
	SLC15A2	NM_021082.4	MANE Select	c.1526G>A	p.Arg509Lys	missense	Exon 17 of 22	NP_066568.3
	SLC15A2	NM_001145998.2		c.1433G>A	p.Arg478Lys	missense	Exon 16 of 21	NP_001139470.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A2	ENST00000489711.6	TSL:1 MANE Select	c.1526G>A	p.Arg509Lys	missense	Exon 17 of 22	ENSP00000417085.1
	SLC15A2	ENST00000966832.1		c.1538G>A	p.Arg513Lys	missense	Exon 17 of 22	ENSP00000636891.1
	SLC15A2	ENST00000886960.1		c.1523G>A	p.Arg508Lys	missense	Exon 17 of 22	ENSP00000557019.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67819 AN: 151936 Hom.: 15674 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.396

GnomAD2 exomes AF: 0.419 AC: 105179 AN: 250802 AF XY: 0.417

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.241

Gnomad ASJ exome AF: 0.379

Gnomad EAS exome AF: 0.717

Gnomad FIN exome AF: 0.409

Gnomad NFE exome AF: 0.455

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.455 AC: 664413 AN: 1460012 Hom.: 155488 Cov.: 38 AF XY: 0.450 AC XY: 326778 AN XY: 726326

African (AFR) AF: 0.487 AC: 16256 AN: 33412

American (AMR) AF: 0.250 AC: 11178 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9935 AN: 26114

East Asian (EAS) AF: 0.723 AC: 28688 AN: 39680

South Asian (SAS) AF: 0.303 AC: 26089 AN: 86120

European-Finnish (FIN) AF: 0.410 AC: 21878 AN: 53374

Middle Eastern (MID) AF: 0.343 AC: 1975 AN: 5766

European-Non Finnish (NFE) AF: 0.470 AC: 522080 AN: 1110568

Other (OTH) AF: 0.436 AC: 26334 AN: 60334

GnomAD4 genome AF: 0.446 AC: 67858 AN: 152054 Hom.: 15684 Cov.: 32 AF XY: 0.437 AC XY: 32503 AN XY: 74352

African (AFR) AF: 0.483 AC: 20042 AN: 41472

American (AMR) AF: 0.307 AC: 4696 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3589 AN: 5178

South Asian (SAS) AF: 0.305 AC: 1471 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4276 AN: 10568

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.456 AC: 31018 AN: 67958

Other (OTH) AF: 0.397 AC: 838 AN: 2110

Alfa AF: 0.454 Hom.: 37662

Bravo AF: 0.447

TwinsUK AF: 0.471 AC: 1747

ALSPAC AF: 0.463 AC: 1786

ESP6500AA AF: 0.488 AC: 2150

ESP6500EA AF: 0.454 AC: 3904

ExAC AF: 0.425 AC: 51642

Asia WGS AF: 0.461 AC: 1602 AN: 3478

EpiCase AF: 0.444

EpiControl AF: 0.442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.25
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.057	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.2	N
PhyloP100		0.12
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.0040
MPC		0.076
ClinPred		0.0026	T
GERP RS		-2.8
Varity_R		0.050
gMVP		0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1143672; hg19: chr3-121648168; COSMIC: COSV107338981; COSMIC: COSV107338981;