Variant chr11-60941256-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016582.3(SLC15A3):c.1142T>C(p.Val381Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,734 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC15A3
NM_016582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.22

Variant links:

Genes affected

SLC15A3 (HGNC:18068): (solute carrier family 15 member 3) Enables dipeptide transmembrane transporter activity. Involved in dipeptide import across plasma membrane. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

SLC15A3 links:

SLC15A3 (HGNC:):

SLC15A3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31178266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A3	NM_016582.3 linkuse as main transcript	c.1142T>C	p.Val381Ala	missense_variant	5/8	ENST00000227880.8	NP_057666.1	Q8IY34
SLC15A3	XM_011545095.3 linkuse as main transcript	c.1142T>C	p.Val381Ala	missense_variant	5/9		XP_011543397.1	A0A7P0T8H0
SLC15A3	NR_027391.2 linkuse as main transcript	n.1732+779T>C		intron_variant
SLC15A3	XR_007062485.1 linkuse as main transcript	n.1732+779T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A3	ENST00000227880.8 linkuse as main transcript	c.1142T>C	p.Val381Ala	missense_variant	5/8	1	NM_016582.3	ENSP00000227880.2		Q8IY34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250940

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461734

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000660

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Jun 16, 2023

The c.1142T>C (p.V381A) alteration is located in exon 5 (coding exon 5) of the SLC15A3 gene. This alteration results from a T to C substitution at nucleotide position 1142, causing the valine (V) at amino acid position 381 to be replaced by an alanine (A). 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

-0.32

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.038

Eigen_PC

Benign

-0.024

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.10

Sift

Benign

0.046

D;D

Sift4G

Uncertain

0.048

D;.

Polyphen

0.025

B;.

Vest4

0.38

MutPred

0.65

Gain of helix (P = 0.2059);.;

MVP

0.47

MPC

0.13

ClinPred

0.28

GERP RS

2.7

Varity_R

0.11

gMVP

0.41

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