Genetic Variant LAX1:p.Thr85Thr (chr1-203771422-C-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_017773.4(LAX1):c.255C>A(p.Thr85Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00266 in 1,614,006 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 59 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 45 hom. )

Consequence

LAX1
NM_017773.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.433

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 1-203771422-C-A is Benign according to our data. Variant chr1-203771422-C-A is described in ClinVar as [Benign]. Clinvar id is 791826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.433 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0134 (2039/152254) while in subpopulation AFR AF= 0.0467 (1941/41524). AF 95% confidence interval is 0.045. There are 59 homozygotes in gnomad4. There are 952 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 59 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAX1	NM_017773.4 link	c.255C>A	p.Thr85Thr	synonymous_variant	Exon 3 of 5	ENST00000442561.7	NP_060243.2	Q8IWV1-1
LAX1	NM_001136190.2 link	c.207C>A	p.Thr69Thr	synonymous_variant	Exon 3 of 5		NP_001129662.1	Q8IWV1-3
LAX1	NM_001282878.1 link	c.27C>A	p.Thr9Thr	synonymous_variant	Exon 3 of 5		NP_001269807.1	Q8IWV1-2
LAX1	XM_006711397.4 link	c.255C>A	p.Thr85Thr	synonymous_variant	Exon 4 of 6		XP_006711460.1	Q8IWV1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAX1	ENST00000442561.7 link	c.255C>A	p.Thr85Thr	synonymous_variant	Exon 3 of 5	1	NM_017773.4	ENSP00000406970.2	Q8IWV1-1
LAX1	ENST00000367215.1 link	n.225C>A		non_coding_transcript_exon_variant	Exon 3 of 5	1
LAX1	ENST00000367217.5 link	c.207C>A	p.Thr69Thr	synonymous_variant	Exon 3 of 5	2		ENSP00000356186.5	Q8IWV1-3

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2040

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0469

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00370

AC:

930

AN:

251480

Hom.:

AF XY:

0.00269

AC XY:

366

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0472

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00155

AC:

2261

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

978

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0500

Gnomad4 AMR exome

AF:

0.00286

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.00313

GnomAD4 genome

AF:

0.0134

AC:

2039

AN:

152254

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

952

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0467

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 30, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.4

DANN

Benign

0.50

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