rs2257212

Variant names:

• chr3-121924957-C-A
• NM_021082.4:c.1048C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-121924957-C-A
• chr3-121924957-C-G
• chr3-121924957-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021082.4(SLC15A2):​c.1048C>A​(p.Leu350Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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. L350F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2899051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A2	NM_021082.4	c.1048C>A	p.Leu350Ile	missense_variant	Exon 13 of 22	ENST00000489711.6	NP_066568.3
SLC15A2	NM_001145998.2	c.955C>A	p.Leu319Ile	missense_variant	Exon 12 of 21		NP_001139470.1
SLC15A2	XM_005247722.4	c.1048C>A	p.Leu350Ile	missense_variant	Exon 13 of 21		XP_005247779.1
SLC15A2	XM_006713736.4	c.1048C>A	p.Leu350Ile	missense_variant	Exon 13 of 19		XP_006713799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A2	ENST00000489711.6	c.1048C>A	p.Leu350Ile	missense_variant	Exon 13 of 22	1	NM_021082.4	ENSP00000417085.1
SLC15A2	ENST00000295605.6	c.955C>A	p.Leu319Ile	missense_variant	Exon 12 of 21	2		ENSP00000295605.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.6
DANN	Benign	0.81
DEOGEN2	Benign	0.049	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.23	N
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.081
Sift	Benign	0.84	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.13	B;.
Vest4		0.10
MutPred		0.42		Loss of helix (P = 0.079);.;
MVP		0.21
MPC		0.099
ClinPred		0.19	T
GERP RS		-5.8
Varity_R		0.12
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr3-121643804;