16-28986400-TGGG-TG

Position:

• chr16-28986400-TGGG-TG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001014987.2(LAT):​c.268_269delGG​(p.Gly90fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LAT NM_001014987.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.29

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-28986400-TGG-T is Pathogenic according to our data. Variant chr16-28986400-TGG-T is described in ClinVar as [Pathogenic]. Clinvar id is 427750.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAT	NM_001014987.2	c.268_269delGG	p.Gly90fs	frameshift_variant	5/12	ENST00000395456.7	NP_001014987.1
LAT	NM_001014989.2	c.376_377delGG	p.Gly126fs	frameshift_variant	6/13		NP_001014989.2
LAT	NM_014387.4	c.268_269delGG	p.Gly90fs	frameshift_variant	5/11		NP_055202.1
LAT	NM_001014988.2	c.265_266delGG	p.Gly89fs	frameshift_variant	5/12		NP_001014988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAT	ENST00000395456.7	c.268_269delGG	p.Gly90fs	frameshift_variant	5/12	1	NM_001014987.2	ENSP00000378841.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Severe combined immunodeficiency due to LAT deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 05, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs781410769; hg19: chr16-28997721;