3-121928439-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021082.4(SLC15A2):​c.1225C>G​(p.Pro409Ala) 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. 13/21 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. P409S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

SLC15A2
NM_021082.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0730
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16087651).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC15A2NM_021082.4 linkuse as main transcriptc.1225C>G p.Pro409Ala missense_variant 15/22 ENST00000489711.6 NP_066568.3 Q16348-1
SLC15A2NM_001145998.2 linkuse as main transcriptc.1132C>G p.Pro378Ala missense_variant 14/21 NP_001139470.1 Q16348-2
SLC15A2XM_005247722.4 linkuse as main transcriptc.1225C>G p.Pro409Ala missense_variant 15/21 XP_005247779.1
SLC15A2XM_006713736.4 linkuse as main transcriptc.1225C>G p.Pro409Ala missense_variant 15/19 XP_006713799.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC15A2ENST00000489711.6 linkuse as main transcriptc.1225C>G p.Pro409Ala missense_variant 15/221 NM_021082.4 ENSP00000417085.1 Q16348-1
SLC15A2ENST00000295605.6 linkuse as main transcriptc.1132C>G p.Pro378Ala missense_variant 14/212 ENSP00000295605.2 Q16348-2
SLC15A2ENST00000465060.1 linkuse as main transcriptn.148C>G non_coding_transcript_exon_variant 1/43
SLC15A2ENST00000489957.1 linkuse as main transcriptn.200C>G non_coding_transcript_exon_variant 2/23

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
42
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
12
DANN
Benign
0.82
DEOGEN2
Benign
0.28
T;.
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.92
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
M;.
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-5.1
D;D
REVEL
Benign
0.046
Sift
Benign
0.034
D;D
Sift4G
Uncertain
0.023
D;D
Polyphen
0.66
P;.
Vest4
0.091
MutPred
0.50
Loss of sheet (P = 0.0181);.;
MVP
0.29
MPC
0.11
ClinPred
0.64
D
GERP RS
-0.53
Varity_R
0.12
gMVP
0.49

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1143671; hg19: chr3-121647286; API