dbSNP rs572112079: LAT:p.Ala18Pro (chr16-28984913-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001014989.2(LAT):c.52G>C(p.Ala18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,394,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

LAT
NM_001014989.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.408

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:

SPNS1 (HGNC:30621): (SPNS lysolipid transporter 1, lysophospholipid) Predicted to enable transmembrane transporter activity. Predicted to be involved in lipid transport and transmembrane transport. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPNS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059369206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAT	NM_001014987.2 link	c.-505G>C		upstream_gene_variant		ENST00000395456.7	NP_001014987.1	O43561-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAT	ENST00000395456.7 link	c.-505G>C		upstream_gene_variant		1	NM_001014987.2	ENSP00000378841.3		O43561-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000714

AC:

AN:

140060

Hom.:

AF XY:

0.00

AC XY:

AN XY:

75444

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:

0.0000448

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000502

AC:

AN:

1394344

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

687794

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:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.80

DANN

Benign

0.82

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.27

M_CAP

Benign

0.0042

MetaRNN

Benign

0.059

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.11

REVEL

Benign

0.034

Sift

Benign

0.16

Sift4G

Benign

0.34

Vest4

0.17

MutPred

0.25

Gain of glycosylation at A18 (P = 0.0136);

MVP

0.14

MPC

0.52

ClinPred

0.078

GERP RS

-1.6

gMVP

0.18

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over