Variant 16-28985482-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001014987.2(LAT):c.65T>C(p.Leu22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,630 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 (★). Synonymous variant affecting the same amino acid position (i.e. L22L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LAT
NM_001014987.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420

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:

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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=0.1938363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LAT	NM_001014987.2 linkuse as main transcript	c.65T>C	p.Leu22Ser	missense_variant	1/12	ENST00000395456.7
LAT	NM_001014989.2 linkuse as main transcript	c.173T>C	p.Leu58Ser	missense_variant	2/13
LAT	NM_014387.4 linkuse as main transcript	c.65T>C	p.Leu22Ser	missense_variant	1/11
LAT	NM_001014988.2 linkuse as main transcript	c.65T>C	p.Leu22Ser	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAT	ENST00000395456.7 linkuse as main transcript	c.65T>C	p.Leu22Ser	missense_variant	1/12	1	NM_001014987.2	P2	O43561-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250910

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135602

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:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461630

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727132

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 26, 2023

The c.173T>C (p.L58S) alteration is located in exon 2 (coding exon 2) of the LAT gene. This alteration results from a T to C substitution at nucleotide position 173, causing the leucine (L) at amino acid position 58 to be replaced by a serine (S). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.63

T;.;T;T;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.0

D;D;.;.;D;D;D;D

REVEL

Benign

0.088

Sift

Pathogenic

0.0

D;D;.;.;D;D;D;D

Sift4G

Uncertain

0.0050

D;D;D;.;D;D;D;D

Polyphen

0.95

.;.;.;.;P;.;P;.

Vest4

0.47

MutPred

0.36

.;Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);Gain of catalytic residue at L22 (P = 0.026);

MVP

0.62

MPC

1.2

ClinPred

0.59

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.45

gMVP

0.62

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