dbSNP rs143269723: LAT:p.Arg31Ser (chr16-28985510-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001014987.2(LAT):c.93A>C(p.Arg31Ser) 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 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 6.8e-7 ( 0 hom. )

Consequence

LAT
NM_001014987.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.581

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:

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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=0.07936028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAT	NM_001014987.2 link	c.93A>C	p.Arg31Ser	missense_variant	Exon 1 of 12	ENST00000395456.7	NP_001014987.1	O43561-2
LAT	NM_001014989.2 link	c.201A>C	p.Arg67Ser	missense_variant	Exon 2 of 13		NP_001014989.2	O43561-3
LAT	NM_014387.4 link	c.93A>C	p.Arg31Ser	missense_variant	Exon 1 of 11		NP_055202.1	O43561-1A0A024QZD6
LAT	NM_001014988.2 link	c.93A>C	p.Arg31Ser	missense_variant	Exon 1 of 12		NP_001014988.1	O43561-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAT	ENST00000395456.7 link	c.93A>C	p.Arg31Ser	missense_variant	Exon 1 of 12	1	NM_001014987.2	ENSP00000378841.3		O43561-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461332

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726940

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Uncertain

0.66

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

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.82

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

M_CAP

Benign

0.0062

MetaRNN

Benign

0.079

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;N;.;.;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.6

D;N;.;.;N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.040

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

Sift4G

Uncertain

0.049

D;D;T;.;D;D;D;D

Polyphen

0.018, 0.79

.;.;.;.;B;.;P;.

Vest4

0.32

MutPred

0.27

.;Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);Gain of disorder (P = 0.055);

MVP

0.25

MPC

0.52

ClinPred

0.25

GERP RS

1.6

Varity_R

0.13

gMVP

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over