Genetic Variant SLC15A5:p.Leu559Val (chr12-16189733-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001170798.1(SLC15A5):c.1675C>G(p.Leu559Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000363 in 1,378,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

SLC15A5
NM_001170798.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

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]

SLC15A5 links:

LOC101928362 (HGNC:):

LOC101928362 links:

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=0.14901048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A5	NM_001170798.1 link	c.1675C>G	p.Leu559Val	missense_variant	Exon 9 of 9	ENST00000344941.3	NP_001164269.1	A6NIM6
LOC101928362	XR_001749028.1 link	n.63-9772G>C		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A5	ENST00000344941.3 link	c.1675C>G	p.Leu559Val	missense_variant	Exon 9 of 9	5	NM_001170798.1	ENSP00000340402.3		A6NIM6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

139638

Hom.:

AF XY:

0.00

AC XY:

AN XY:

74820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000363

AC:

AN:

1378294

Hom.:

Cov.:

AF XY:

0.00000441

AC XY:

AN XY:

679874

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:

0.00000465

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000444

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1675C>G (p.L559V) alteration is located in exon 9 (coding exon 9) of the SLC15A5 gene. This alteration results from a C to G substitution at nucleotide position 1675, causing the leucine (L) at amino acid position 559 to be replaced by a valine (V). 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

0.096

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0064

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.60

M_CAP

Benign

0.010

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.86

REVEL

Benign

0.058

Sift

Uncertain

0.020

Sift4G

Uncertain

0.050

Vest4

0.10

MutPred

0.35

Gain of catalytic residue at L554 (P = 9e-04);

MVP

0.055

ClinPred

0.80

GERP RS

4.8

Varity_R

0.15

gMVP

0.69

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over