chr16-28985404-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001014989.2(LAT):c.95G>A(p.Arg32Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,613,142 control chromosomes in the GnomAD database, including 80 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 38 hom. )

Consequence

LAT
NM_001014989.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.24

Variant links:

Genes affected

LAT (HGNC:18874): (linker for activation of T cells) The protein encoded by this gene is phosphorylated by ZAP-70/Syk protein tyrosine kinases following activation of the T-cell antigen receptor (TCR) signal transduction pathway. This transmembrane protein localizes to lipid rafts and acts as a docking site for SH2 domain-containing proteins. Upon phosphorylation, this protein recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

LAT links:

ENSG00000261067 (HGNC:):

ENSG00000261067 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002146989).

BP6

Variant 16-28985404-G-A is Benign according to our data. Variant chr16-28985404-G-A is described in ClinVar as [Benign]. Clinvar id is 777001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1958/152264) while in subpopulation AFR AF= 0.0444 (1846/41554). AF 95% confidence interval is 0.0427. There are 42 homozygotes in gnomad4. There are 934 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAT	NM_001014987.2 link	c.-14G>A		5_prime_UTR_variant	Exon 1 of 12	ENST00000395456.7	NP_001014987.1	O43561-2
LAT	NM_001014989.2 link	c.95G>A	p.Arg32Gln	missense_variant	Exon 2 of 13		NP_001014989.2	O43561-3
LAT	NM_014387.4 link	c.-14G>A		5_prime_UTR_variant	Exon 1 of 11		NP_055202.1	O43561-1A0A024QZD6
LAT	NM_001014988.2 link	c.-14G>A		5_prime_UTR_variant	Exon 1 of 12		NP_001014988.1	O43561-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAT	ENST00000395456 link	c.-14G>A		5_prime_UTR_variant	Exon 1 of 12	1	NM_001014987.2	ENSP00000378841.3		O43561-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1956

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00347

AC:

870

AN:

250448

Hom.:

AF XY:

0.00234

AC XY:

317

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00136

AC:

1993

AN:

1460878

Hom.:

Cov.:

AF XY:

0.00117

AC XY:

849

AN XY:

726766

show subpopulations

Gnomad4 AFR exome

AF:

0.0473

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.00322

GnomAD4 genome

AF:

0.0129

AC:

1958

AN:

152264

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

934

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0444

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00537

Hom.:

Bravo

AF:

0.0150

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0471

AC:

207

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00425

AC:

516

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.8

DANN

Uncertain

1.0

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.12

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Benign

0.54

Vest4

0.070

MVP

0.095

MPC

0.75

ClinPred

0.038

GERP RS

-0.085

gMVP

0.16

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