chr1-203773957-C-T

Variant names:

• chr1-203773957-C-T
• NM_017773.4:c.473C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017773.4(LAX1):​c.473C>T​(p.Ala158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: LAX1 NM_017773.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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]

ACMG classification

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=0.13413313).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAX1	NM_017773.4	c.473C>T	p.Ala158Val	missense_variant	Exon 5 of 5	ENST00000442561.7	NP_060243.2
LAX1	NM_001136190.2	c.425C>T	p.Ala142Val	missense_variant	Exon 5 of 5		NP_001129662.1
LAX1	NM_001282878.1	c.245C>T	p.Ala82Val	missense_variant	Exon 5 of 5		NP_001269807.1
LAX1	XM_006711397.4	c.473C>T	p.Ala158Val	missense_variant	Exon 6 of 6		XP_006711460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAX1	ENST00000442561.7	c.473C>T	p.Ala158Val	missense_variant	Exon 5 of 5	1	NM_017773.4	ENSP00000406970.2
LAX1	ENST00000367215.1	n.443C>T		non_coding_transcript_exon_variant	Exon 5 of 5	1
LAX1	ENST00000367217.5	c.425C>T	p.Ala142Val	missense_variant	Exon 5 of 5	2		ENSP00000356186.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473C>T (p.A158V) alteration is located in exon 5 (coding exon 5) of the LAX1 gene. This alteration results from a C to T substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.070
Sift	Benign	0.10	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.73	P;.
Vest4		0.16
MutPred		0.26		Gain of phosphorylation at Y155 (P = 0.1768);.;
MVP		0.58
MPC		0.50
ClinPred		0.75	D
GERP RS		3.6
Varity_R		0.060
gMVP		0.024

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.

Other links and lift over

hg19: chr1-203743085;