chr12-128823636-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_145648.4(SLC15A4):c.308C>T(p.Ala103Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000648 in 1,482,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
SLC15A4
NM_145648.4 missense
NM_145648.4 missense
Scores
1
2
16
Clinical Significance
Conservation
PhyloP100: 4.05
Genes affected
SLC15A4 (HGNC:23090): (solute carrier family 15 member 4) Enables L-histidine transmembrane transporter activity; peptide transmembrane transporter activity; and peptidoglycan transmembrane transporter activity. Involved in several processes, including dipeptide import across plasma membrane; peptidoglycan transport; and positive regulation of toll-like receptor signaling pathway. Located in endolysosome membrane. Is integral component of lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]
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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=0.23024175).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC15A4 | NM_145648.4 | c.308C>T | p.Ala103Val | missense_variant | 1/8 | ENST00000266771.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC15A4 | ENST00000266771.10 | c.308C>T | p.Ala103Val | missense_variant | 1/8 | 1 | NM_145648.4 | P1 | |
SLC15A4 | ENST00000376744.8 | c.146C>T | p.Ala49Val | missense_variant, NMD_transcript_variant | 1/7 | 2 | |||
SLC15A4 | ENST00000539703.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000396 AC: 6AN: 151636Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000683 AC: 6AN: 87788Hom.: 0 AF XY: 0.0000605 AC XY: 3AN XY: 49622
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GnomAD4 exome AF: 0.0000676 AC: 90AN: 1330448Hom.: 0 Cov.: 31 AF XY: 0.0000625 AC XY: 41AN XY: 655840
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GnomAD4 genome ? AF: 0.0000396 AC: 6AN: 151636Hom.: 0 Cov.: 33 AF XY: 0.0000405 AC XY: 3AN XY: 74070
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.308C>T (p.A103V) alteration is located in exon 1 (coding exon 1) of the SLC15A4 gene. This alteration results from a C to T substitution at nucleotide position 308, causing the alanine (A) at amino acid position 103 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of helix (P = 0.0626);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at