3-121929321-G-C

Variant names:

• chr3-121929321-G-C
• NM_021082.4:c.1526G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021082.4(SLC15A2):​c.1526G>C​(p.Arg509Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R509K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062218875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A2	NM_021082.4	c.1526G>C	p.Arg509Thr	missense_variant	Exon 17 of 22	ENST00000489711.6	NP_066568.3
SLC15A2	NM_001145998.2	c.1433G>C	p.Arg478Thr	missense_variant	Exon 16 of 21		NP_001139470.1
SLC15A2	XM_005247722.4	c.1526G>C	p.Arg509Thr	missense_variant	Exon 17 of 21		XP_005247779.1
SLC15A2	XM_006713736.4	c.1526G>C	p.Arg509Thr	missense_variant	Exon 17 of 19		XP_006713799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1526G>C	p.Arg509Thr	missense_variant	Exon 17 of 22	1	NM_021082.4	ENSP00000417085.1
SLC15A2	ENST00000295605.6	c.1433G>C	p.Arg478Thr	missense_variant	Exon 16 of 21	2		ENSP00000295605.2
SLC15A2	ENST00000465060.1	n.449G>C		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727084

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Benign	0.89
DEOGEN2	Uncertain	0.51	D;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.041
Sift	Uncertain	0.019	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0	B;.
Vest4		0.046
MutPred		0.40		Loss of MoRF binding (P = 0.0466);.;
MVP		0.16
MPC		0.11
ClinPred		0.079	T
GERP RS		-2.8
Varity_R		0.092
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-121648168;