Genetic Variant NM_001170798.1:c.781G>T (chr12-16244774-C-A) – 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.781G>T(p.Val261Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000455 in 1,537,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

SLC15A5
NM_001170798.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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:

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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=0.0818198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A5	NM_001170798.1 link	c.781G>T	p.Val261Leu	missense_variant	Exon 4 of 9	ENST00000344941.3	NP_001164269.1	A6NIM6
LOC101928362	XR_001749028.1 link	n.334-57C>A		intron_variant	Intron 4 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A5	ENST00000344941.3 link	c.781G>T	p.Val261Leu	missense_variant	Exon 4 of 9	5	NM_001170798.1	ENSP00000340402.3		A6NIM6

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000624

AC:

AN:

144152

Hom.:

AF XY:

0.0000652

AC XY:

AN XY:

76656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000406

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000880

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000516

Gnomad OTH exome

AF:

0.000457

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1385400

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

683590

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:

0.0000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000417

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000840

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.781G>T (p.V261L) alteration is located in exon 4 (coding exon 4) of the SLC15A5 gene. This alteration results from a G to T substitution at nucleotide position 781, causing the valine (V) at amino acid position 261 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

M_CAP

Benign

0.019

MetaRNN

Benign

0.082

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.9

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Benign

0.087

Sift4G

Uncertain

0.025

Vest4

0.47

MutPred

0.56

Gain of catalytic residue at S264 (P = 2e-04);

MVP

0.048

ClinPred

0.30

GERP RS

5.0

Varity_R

0.34

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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