NM_021082.4:c.1161A>G

Variant names:

• chr3-121927794-A-G
• rs1143670
• NM_021082.4:c.1161A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021082.4(SLC15A2):​c.1161A>G​(p.Ala387Ala) 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 NM_021082.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.468
• Publications: 32 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 -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.

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.1161A>G	p.Ala387Ala	synonymous	Exon 14 of 22	NP_066568.3
	SLC15A2	NM_001145998.2		c.1068A>G	p.Ala356Ala	synonymous	Exon 13 of 21	NP_001139470.1	Q16348-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC15A2	ENST00000489711.6	TSL:1 MANE Select	c.1161A>G	p.Ala387Ala	synonymous	Exon 14 of 22	ENSP00000417085.1	Q16348-1
	SLC15A2	ENST00000966832.1		c.1173A>G	p.Ala391Ala	synonymous	Exon 14 of 22	ENSP00000636891.1
	SLC15A2	ENST00000886960.1		c.1158A>G	p.Ala386Ala	synonymous	Exon 14 of 22	ENSP00000557019.1

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

GnomAD2 exomes AF: 0.416 AC: 104584 AN: 251142 AF XY: 0.414

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 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

African (AFR) AF: 0.441 AC: 14747 AN: 33428

American (AMR) AF: 0.249 AC: 11150 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9932 AN: 26112

East Asian (EAS) AF: 0.723 AC: 28688 AN: 39684

South Asian (SAS) AF: 0.303 AC: 26086 AN: 86146

European-Finnish (FIN) AF: 0.410 AC: 21876 AN: 53372

Middle Eastern (MID) AF: 0.342 AC: 1971 AN: 5764

European-Non Finnish (NFE) AF: 0.470 AC: 521494 AN: 1109566

Other (OTH) AF: 0.434 AC: 26171 AN: 60300

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

African (AFR) AF: 0.442 AC: 18312 AN: 41476

American (AMR) AF: 0.305 AC: 4651 AN: 15274

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

East Asian (EAS) AF: 0.693 AC: 3589 AN: 5180

South Asian (SAS) AF: 0.305 AC: 1466 AN: 4812

European-Finnish (FIN) AF: 0.405 AC: 4270 AN: 10552

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

European-Non Finnish (NFE) AF: 0.456 AC: 31011 AN: 67978

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.445 Hom.: 45070

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.47
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1143670; hg19: chr3-121646641; COSMIC: COSV108087072; COSMIC: COSV108087072;