NM_001170798.1:c.1457T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001170798.1(SLC15A5):​c.1457T>A​(p.Val486Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000722 in 1,384,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLC15A5
NM_001170798.1 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41
Variant links:
Genes affected
SLC15A5 (HGNC:33455): (solute carrier family 15 member 5) Predicted to enable symporter activity. Predicted to be involved in peptide transport; protein transport; and transmembrane transport. Predicted to be integral component of 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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC15A5NM_001170798.1 linkc.1457T>A p.Val486Glu missense_variant Exon 7 of 9 ENST00000344941.3 NP_001164269.1 A6NIM6
LOC101928362XR_001749028.1 linkn.204-16162A>T intron_variant Intron 2 of 10

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC15A5ENST00000344941.3 linkc.1457T>A p.Val486Glu missense_variant Exon 7 of 9 5 NM_001170798.1 ENSP00000340402.3 A6NIM6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.22e-7
AC:
1
AN:
1384432
Hom.:
0
Cov.:
33
AF XY:
0.00000146
AC XY:
1
AN XY:
683110
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
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
Aug 17, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1457T>A (p.V486E) alteration is located in exon 7 (coding exon 7) of the SLC15A5 gene. This alteration results from a T to A substitution at nucleotide position 1457, causing the valine (V) at amino acid position 486 to be replaced by a glutamic acid (E). 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
Uncertain
0.36
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
25
DANN
Uncertain
0.98
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.59
T
M_CAP
Uncertain
0.086
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.35
T
MutationAssessor
Pathogenic
3.4
M
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.6
D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0040
D
Vest4
0.77
MutPred
0.59
Gain of catalytic residue at T481 (P = 0);
MVP
0.21
ClinPred
0.97
D
GERP RS
5.2
Varity_R
0.85
gMVP
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr12-16369853; API