3-121924957-C-T

Position:

• chr3-121924957-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021082.4(SLC15A2):​c.1048C>T​(p.Leu350Phe) 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 1,605,712 control chromosomes in the GnomAD database, including 170,349 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 (15661 hom., cov: 31)
  • Exomes 𝑓: 0.45 (154688 hom.)
• Consequence: SLC15A2 NM_021082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152

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=1.3313554E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC15A2	NM_021082.4	c.1048C>T	p.Leu350Phe	missense_variant	13/22	ENST00000489711.6
SLC15A2	NM_001145998.2	c.955C>T	p.Leu319Phe	missense_variant	12/21
SLC15A2	XM_005247722.4	c.1048C>T	p.Leu350Phe	missense_variant	13/21
SLC15A2	XM_006713736.4	c.1048C>T	p.Leu350Phe	missense_variant	13/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1048C>T	p.Leu350Phe	missense_variant	13/22	1	NM_021082.4	P1
SLC15A2	ENST00000295605.6	c.955C>T	p.Leu319Phe	missense_variant	12/21	2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67755 AN: 151794 Hom.: 15651 Cov.: 31

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.396

GnomAD3 exomes AF: 0.420 AC: 105436 AN: 251312 Hom.: 24009 AF XY: 0.417 AC XY: 56619 AN XY: 135830

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.242

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: 0.394

GnomAD4 exome AF: 0.454 AC: 660511 AN: 1453800 Hom.: 154688 Cov.: 32 AF XY: 0.449 AC XY: 325086 AN XY: 723634

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.251

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: 0.469

Gnomad4 OTH exome AF: 0.436

GnomAD4 genome AF: 0.446 AC: 67794 AN: 151912 Hom.: 15661 Cov.: 31 AF XY: 0.437 AC XY: 32463 AN XY: 74238

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.397

Alfa AF: 0.446 Hom.: 39660

Bravo AF: 0.447

TwinsUK AF: 0.472 AC: 1751

ALSPAC AF: 0.463 AC: 1784

ESP6500AA AF: 0.487 AC: 2145

ESP6500EA AF: 0.453 AC: 3899

ExAC AF: 0.425 AC: 51643

Asia WGS AF: 0.461 AC: 1601 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	0.059
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0000013	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.00037	P;P
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.10
Sift	Benign	0.27	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.060	B;.
Vest4		0.022
MPC		0.10
ClinPred		0.028	T
GERP RS		-5.8
Varity_R		0.12
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2257212; hg19: chr3-121643804; COSMIC: COSV55195908; COSMIC: COSV55195908;