Variant 1-203774332-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017773.4(LAX1):c.848A>G(p.Gln283Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

LAX1
NM_017773.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.178

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:

Genome browser will be placed here

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=0.0442518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LAX1	NM_017773.4 linkuse as main transcript	c.848A>G	p.Gln283Arg	missense_variant	5/5	ENST00000442561.7	NP_060243.2
LAX1	NM_001136190.2 linkuse as main transcript	c.800A>G	p.Gln267Arg	missense_variant	5/5		NP_001129662.1
LAX1	NM_001282878.1 linkuse as main transcript	c.620A>G	p.Gln207Arg	missense_variant	5/5		NP_001269807.1
LAX1	XM_006711397.4 linkuse as main transcript	c.848A>G	p.Gln283Arg	missense_variant	6/6		XP_006711460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAX1	ENST00000442561.7 linkuse as main transcript	c.848A>G	p.Gln283Arg	missense_variant	5/5	1	NM_017773.4	ENSP00000406970	P2	Q8IWV1-1
LAX1	ENST00000367215.1 linkuse as main transcript	n.818A>G		non_coding_transcript_exon_variant	5/5	1
LAX1	ENST00000367217.5 linkuse as main transcript	c.800A>G	p.Gln267Arg	missense_variant	5/5	2		ENSP00000356186	A2	Q8IWV1-3

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251284

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000185

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000112

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

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

Jul 12, 2022

The c.848A>G (p.Q283R) alteration is located in exon 5 (coding exon 5) of the LAX1 gene. This alteration results from a A to G substitution at nucleotide position 848, causing the glutamine (Q) at amino acid position 283 to be replaced by an arginine (R). 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

Benign

0.11

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.6

DANN

Benign

0.89

DEOGEN2

Benign

0.16

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.044

Sift

Benign

0.35

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.011

B;.

Vest4

0.080

MVP

0.37

MPC

0.20

ClinPred

0.014

GERP RS

0.27

Varity_R

0.028

gMVP

0.049

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