chr3-121927794-A-G

Position:

• chr3-121927794-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000489711.6(SLC15A2):​c.1161A>G​(p.Ala387=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 1,611,122 control chromosomes in the GnomAD database, including 169,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (14866 hom., cov: 32)
  • Exomes 𝑓: 0.45 (154612 hom.)
• Consequence: SLC15A2 ENST00000489711.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=-0.468 with no splicing effect.
• 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	Protein	UniProt
SLC15A2	NM_021082.4	c.1161A>G	p.Ala387=	synonymous_variant	14/22	ENST00000489711.6	NP_066568.3
SLC15A2	NM_001145998.2	c.1068A>G	p.Ala356=	synonymous_variant	13/21		NP_001139470.1
SLC15A2	XM_005247722.4	c.1161A>G	p.Ala387=	synonymous_variant	14/21		XP_005247779.1
SLC15A2	XM_006713736.4	c.1161A>G	p.Ala387=	synonymous_variant	14/19		XP_006713799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1161A>G	p.Ala387=	synonymous_variant	14/22	1	NM_021082.4	ENSP00000417085	P1
SLC15A2	ENST00000295605.6	c.1068A>G	p.Ala356=	synonymous_variant	13/21	2		ENSP00000295605
SLC15A2	ENST00000489957.1	n.136A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.434 AC: 66005 AN: 151936 Hom.: 14857 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.416 AC: 104584 AN: 251142 Hom.: 23630 AF XY: 0.414 AC XY: 56247 AN XY: 135732

Gnomad AFR exome AF: 0.441

Gnomad AMR exome AF: 0.240

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: 0.454 AC: 662115 AN: 1459068 Hom.: 154612 Cov.: 35 AF XY: 0.449 AC XY: 325793 AN XY: 725980

Gnomad4 AFR exome AF: 0.441

Gnomad4 AMR exome AF: 0.249

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: 0.434

GnomAD4 genome AF: 0.434 AC: 66045 AN: 152054 Hom.: 14866 Cov.: 32 AF XY: 0.426 AC XY: 31643 AN XY: 74330

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.305

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: 0.388

Alfa AF: 0.444 Hom.: 34028

Bravo AF: 0.434

Asia WGS AF: 0.457 AC: 1589 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
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.1
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1143670; hg19: chr3-121646641;