chr3-121929321-G-A

Position:

• chr3-121929321-G-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A2	NM_021082.4	c.1526G>A	p.Arg509Lys	missense_variant	17/22	ENST00000489711.6
SLC15A2	NM_001145998.2	c.1433G>A	p.Arg478Lys	missense_variant	16/21
SLC15A2	XM_005247722.4	c.1526G>A	p.Arg509Lys	missense_variant	17/21
SLC15A2	XM_006713736.4	c.1526G>A	p.Arg509Lys	missense_variant	17/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1526G>A	p.Arg509Lys	missense_variant	17/22	1	NM_021082.4	P1
SLC15A2	ENST00000295605.6	c.1433G>A	p.Arg478Lys	missense_variant	16/21	2
SLC15A2	ENST00000465060.1	n.449G>A		non_coding_transcript_exon_variant	3/4	3

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

GnomAD3 exomes AF: 0.419 AC: 105179 AN: 250802 Hom.: 23978 AF XY: 0.417 AC XY: 56465 AN XY: 135534

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 SAS exome AF: 0.299

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

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.380

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.436

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

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.397

Alfa AF: 0.455 Hom.: 27815

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 v4.3

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;T
MetaRNN	Benign	0.0000033	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-2.2	N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	2.6	N;N
REVEL	Benign	0.053
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1143672; hg19: chr3-121648168;