Variant 4-4279506-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000343470.9(LYAR):c.370G>C(p.Val124Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LYAR
ENST00000343470.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.88

Variant links:

Genes affected

LYAR (HGNC:26021): (Ly1 antibody reactive) Enables several functions, including DNA-binding transcription factor binding activity; identical protein binding activity; and transcription regulator inhibitor activity. Involved in several processes, including erythrocyte development; negative regulation of innate immune response; and regulation of transcription, DNA-templated. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LYAR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07400668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LYAR	NM_017816.3 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	6/10	ENST00000343470.9	NP_060286.1
LYAR	NM_001145725.2 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	6/10		NP_001139197.1
LYAR	XM_011513505.2 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	6/10		XP_011511807.1
LYAR	XM_011513506.4 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	5/9		XP_011511808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYAR	ENST00000343470.9 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	6/10	1	NM_017816.3	ENSP00000345917	P1
LYAR	ENST00000452476.5 linkuse as main transcript	c.370G>C	p.Val124Leu	missense_variant	6/10	1		ENSP00000397367	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251136

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460196

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726560

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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 16, 2023

The c.370G>C (p.V124L) alteration is located in exon 6 (coding exon 4) of the LYAR gene. This alteration results from a G to C substitution at nucleotide position 370, causing the valine (V) at amino acid position 124 to be replaced by a leucine (L). 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

Uncertain

0.45

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0060

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.032

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.015

D;D

Vest4

0.38

MutPred

0.28

Gain of catalytic residue at V124 (P = 0.0451);Gain of catalytic residue at V124 (P = 0.0451);

MVP

0.20

MPC

0.054

ClinPred

0.87

GERP RS

2.6

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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