Variant 1-203774296-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 ENST00000442561.7(LAX1):c.812T>C(p.Met271Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

LAX1
ENST00000442561.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.18

Variant links:

Genes affected

LAX1 (HGNC:26005): (lymphocyte transmembrane adaptor 1) Enables SH2 domain binding activity and protein kinase binding activity. Involved in several processes, including B cell activation; negative regulation of MAP kinase activity; and negative regulation of T cell activation. Located in Golgi apparatus; cytosol; and plasma membrane. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAX1 links:

LAX1 (HGNC:):

LAX1 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=0.25687236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAX1	NM_017773.4 linkuse as main transcript	c.812T>C	p.Met271Thr	missense_variant	5/5	ENST00000442561.7	NP_060243.2	Q8IWV1-1
LAX1	NM_001136190.2 linkuse as main transcript	c.764T>C	p.Met255Thr	missense_variant	5/5		NP_001129662.1	Q8IWV1-3
LAX1	NM_001282878.1 linkuse as main transcript	c.584T>C	p.Met195Thr	missense_variant	5/5		NP_001269807.1	Q8IWV1-2
LAX1	XM_006711397.4 linkuse as main transcript	c.812T>C	p.Met271Thr	missense_variant	6/6		XP_006711460.1	Q8IWV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAX1	ENST00000442561.7 linkuse as main transcript	c.812T>C	p.Met271Thr	missense_variant	5/5	1	NM_017773.4	ENSP00000406970.2	Q8IWV1-1
LAX1	ENST00000367215.1 linkuse as main transcript	n.782T>C		non_coding_transcript_exon_variant	5/5	1
LAX1	ENST00000367217.5 linkuse as main transcript	c.764T>C	p.Met255Thr	missense_variant	5/5	2		ENSP00000356186.5	Q8IWV1-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251320

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135838

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:

0.00000880

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727242

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:

0.00000809

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

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

Feb 27, 2024

The c.812T>C (p.M271T) alteration is located in exon 5 (coding exon 5) of the LAX1 gene. This alteration results from a T to C substitution at nucleotide position 812, causing the methionine (M) at amino acid position 271 to be replaced by a threonine (T). 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

Uncertain

0.41

BayesDel_addAF

Uncertain

0.014

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.61

D;.

Eigen

Benign

-0.030

Eigen_PC

Benign

0.066

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

0.54

N;N

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.2

D;D

REVEL

Benign

0.10

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.32

B;.

Vest4

0.27

MutPred

0.30

Gain of glycosylation at M271 (P = 0.0278);.;

MVP

0.50

MPC

0.17

ClinPred

0.55

GERP RS

4.2

Varity_R

0.37

gMVP

0.085

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