Variant 11-60937242-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_016582.3(SLC15A3):c.1723C>T(p.Arg575Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SLC15A3
NM_016582.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.723

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.006957382).

BP6

Variant 11-60937242-G-A is Benign according to our data. Variant chr11-60937242-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3163017.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC15A3	NM_016582.3 linkuse as main transcript	c.1723C>T	p.Arg575Cys	missense_variant	8/8	ENST00000227880.8	NP_057666.1	Q8IY34
SLC15A3	XM_011545095.3 linkuse as main transcript	c.*166C>T		3_prime_UTR_variant	9/9		XP_011543397.1	A0A7P0T8H0
SLC15A3	NR_027391.2 linkuse as main transcript	n.2179C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC15A3	ENST00000227880.8 linkuse as main transcript	c.1723C>T	p.Arg575Cys	missense_variant	8/8	1	NM_016582.3	ENSP00000227880.2		Q8IY34

Frequencies

GnomAD3 genomes

AF:

0.000374

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000995

AC:

AN:

251136

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0000289

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:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.0000330

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000374

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000694

Hom.:

Bravo

AF:

0.000434

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.12

DANN

Benign

0.82

DEOGEN2

Benign

0.00037

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.34

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.3

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.030

REVEL

Benign

0.022

Sift

Benign

0.080

Sift4G

Benign

0.081

Polyphen

0.0

Vest4

0.048

MVP

0.081

MPC

0.13

ClinPred

0.010

GERP RS

-7.7

Varity_R

0.036

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