Variant 1-203774418-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017773.4(LAX1):c.934G>A(p.Asp312Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000279 in 1,614,232 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 3 hom. )

Consequence

LAX1
NM_017773.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058870614).

BP6

Variant 1-203774418-G-A is Benign according to our data. Variant chr1-203774418-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 711779.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LAX1	NM_017773.4 linkuse as main transcript	c.934G>A	p.Asp312Asn	missense_variant	5/5	ENST00000442561.7	NP_060243.2
LAX1	NM_001136190.2 linkuse as main transcript	c.886G>A	p.Asp296Asn	missense_variant	5/5		NP_001129662.1
LAX1	NM_001282878.1 linkuse as main transcript	c.706G>A	p.Asp236Asn	missense_variant	5/5		NP_001269807.1
LAX1	XM_006711397.4 linkuse as main transcript	c.934G>A	p.Asp312Asn	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.934G>A	p.Asp312Asn	missense_variant	5/5	1	NM_017773.4	ENSP00000406970	P2	Q8IWV1-1
LAX1	ENST00000367215.1 linkuse as main transcript	n.904G>A		non_coding_transcript_exon_variant	5/5	1
LAX1	ENST00000367217.5 linkuse as main transcript	c.886G>A	p.Asp296Asn	missense_variant	5/5	2		ENSP00000356186	A2	Q8IWV1-3

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

226

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

GnomAD3 exomes

AF:

0.000422

AC:

106

AN:

251428

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.000173

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:

0.000154

AC:

225

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00600

Gnomad4 AMR exome

AF:

0.000179

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:

0.00000899

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.00148

AC:

226

AN:

152340

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00529

Gnomad4 AMR

AF:

0.000392

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:

0.00

Alfa

AF:

0.000302

Hom.:

Bravo

AF:

0.00174

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000535

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.0059

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.096

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.094

T;T

Polyphen

0.19

B;.

Vest4

0.071

MVP

0.52

MPC

0.12

ClinPred

0.035

GERP RS

4.6

Varity_R

0.056

gMVP

0.014

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