chr3-121894547-C-T

Variant summary

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

The NM_021082.4(SLC15A2):​c.71C>T​(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SLC15A2
NM_021082.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15
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]

Genome browser will be placed here

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=0.14251617).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC15A2NM_021082.4 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 22 ENST00000489711.6 NP_066568.3 Q16348-1
SLC15A2NM_001145998.2 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 21 NP_001139470.1 Q16348-2
SLC15A2XM_005247722.4 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 21 XP_005247779.1
SLC15A2XM_006713736.4 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 19 XP_006713799.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC15A2ENST00000489711.6 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 22 1 NM_021082.4 ENSP00000417085.1 Q16348-1
SLC15A2ENST00000295605.6 linkc.71C>T p.Pro24Leu missense_variant Exon 1 of 21 2 ENSP00000295605.2 Q16348-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461762
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.71C>T (p.P24L) alteration is located in exon 1 (coding exon 1) of the SLC15A2 gene. This alteration results from a C to T substitution at nucleotide position 71, causing the proline (P) at amino acid position 24 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.17
T;.
Eigen
Benign
-0.65
Eigen_PC
Benign
-0.61
FATHMM_MKL
Benign
0.092
N
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.0086
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.9
L;L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.3
N;N
REVEL
Benign
0.033
Sift
Benign
0.25
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.31
B;.
Vest4
0.31
MutPred
0.32
Loss of glycosylation at P24 (P = 0.0076);Loss of glycosylation at P24 (P = 0.0076);
MVP
0.18
MPC
0.12
ClinPred
0.78
D
GERP RS
4.2
Varity_R
0.043
gMVP
0.56

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: chr3-121613394; API