Variant 11-111549734-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178834.5(LAYN):c.500G>A(p.Arg167Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000117 in 1,453,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

LAYN
NM_178834.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

Variant links:

Genes affected

LAYN (HGNC:29471): (layilin) Enables hyaluronic acid binding activity. Located in focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

LAYN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27851284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAYN	NM_178834.5 link	c.500G>A	p.Arg167Gln	missense_variant	3/7	ENST00000375614.7	NP_849156.1	Q6UX15-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAYN	ENST00000375614.7 link	c.500G>A	p.Arg167Gln	missense_variant	3/7	1	NM_178834.5	ENSP00000364764.2		Q6UX15-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000247

AC:

AN:

242478

Hom.:

AF XY:

0.00000763

AC XY:

AN XY:

131130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000624

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000901

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1453236

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

722544

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000464

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000103

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000832

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

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 28, 2023

The c.500G>A (p.R167Q) alteration is located in exon 3 (coding exon 3) of the LAYN gene. This alteration results from a G to A substitution at nucleotide position 500, causing the arginine (R) at amino acid position 167 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;.;T;T;T;T

Eigen

Benign

0.0063

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.91

D;D;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.28

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;.;L;.;.;.

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

D;N;N;N;N;D

REVEL

Benign

0.071

Sift

Benign

0.055

T;D;D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D;D;D

Polyphen

0.39, 0.80, 0.72

.;B;P;P;P;.

Vest4

0.16, 0.17, 0.17, 0.24

MutPred

0.48

.;.;Gain of ubiquitination at K179 (P = 0.1047);Gain of ubiquitination at K179 (P = 0.1047);.;.;

MVP

0.36

MPC

0.25

ClinPred

0.41

GERP RS

2.5

Varity_R

0.13

gMVP

0.46

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