3-121928439-C-T

Variant names:

• chr3-121928439-C-T
• rs1143671
• NM_021082.4:c.1225C>T

Variant summary

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

The NM_021082.4(SLC15A2):​c.1225C>T​(p.Pro409Ser) 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 1,613,116 control chromosomes in the GnomAD database, including 171,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 (15682 hom., cov: 32)
  • Exomes 𝑓: 0.46 (155488 hom.)
• Consequence: SLC15A2 NM_021082.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 69 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=3.0575927E-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 rank	MANE	Protein	UniProt
SLC15A2	NM_021082.4	c.1225C>T	p.Pro409Ser	missense_variant	Exon 15 of 22	ENST00000489711.6	NP_066568.3
SLC15A2	NM_001145998.2	c.1132C>T	p.Pro378Ser	missense_variant	Exon 14 of 21		NP_001139470.1
SLC15A2	XM_005247722.4	c.1225C>T	p.Pro409Ser	missense_variant	Exon 15 of 21		XP_005247779.1
SLC15A2	XM_006713736.4	c.1225C>T	p.Pro409Ser	missense_variant	Exon 15 of 19		XP_006713799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1225C>T	p.Pro409Ser	missense_variant	Exon 15 of 22	1	NM_021082.4	ENSP00000417085.1
SLC15A2	ENST00000295605.6	c.1132C>T	p.Pro378Ser	missense_variant	Exon 14 of 21	2		ENSP00000295605.2
SLC15A2	ENST00000465060.1	n.148C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3
SLC15A2	ENST00000489957.1	n.200C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67791 AN: 151830 Hom.: 15672 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.397

GnomAD2 exomes AF: 0.420 AC: 105319 AN: 251004 AF XY: 0.417

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 FIN exome AF: 0.409

Gnomad NFE exome AF: 0.456

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.455 AC: 665020 AN: 1461168 Hom.: 155488 Cov.: 42 AF XY: 0.450 AC XY: 327054 AN XY: 726888

African (AFR) AF: 0.487 AC: 16281 AN: 33462

American (AMR) AF: 0.251 AC: 11209 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 9935 AN: 26110

East Asian (EAS) AF: 0.723 AC: 28689 AN: 39686

South Asian (SAS) AF: 0.303 AC: 26138 AN: 86210

European-Finnish (FIN) AF: 0.410 AC: 21882 AN: 53392

Middle Eastern (MID) AF: 0.343 AC: 1976 AN: 5764

European-Non Finnish (NFE) AF: 0.470 AC: 522566 AN: 1111492

Other (OTH) AF: 0.436 AC: 26344 AN: 60358

GnomAD4 genome AF: 0.446 AC: 67830 AN: 151948 Hom.: 15682 Cov.: 32 AF XY: 0.438 AC XY: 32491 AN XY: 74260

African (AFR) AF: 0.483 AC: 20015 AN: 41430

American (AMR) AF: 0.307 AC: 4691 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3585 AN: 5168

South Asian (SAS) AF: 0.305 AC: 1470 AN: 4814

European-Finnish (FIN) AF: 0.406 AC: 4284 AN: 10544

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31020 AN: 67946

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.449 Hom.: 60233

Bravo AF: 0.447

TwinsUK AF: 0.472 AC: 1750

ALSPAC AF: 0.463 AC: 1786

ESP6500AA AF: 0.488 AC: 2150

ESP6500EA AF: 0.454 AC: 3905

ExAC AF: 0.425 AC: 51650

Asia WGS AF: 0.461 AC: 1603 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	0.11
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.0000031	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		-0.073
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Benign	0.048
Sift	Benign	0.038	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.96	D;.
Vest4		0.021
MPC		0.18
ClinPred		0.041	T
GERP RS		-0.53
Varity_R		0.13
gMVP		0.62
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143671; hg19: chr3-121647286; COSMIC: COSV107338980;