Variant 4-4281847-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000343470.9(LYAR):c.173A>T(p.Tyr58Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,614,200 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LYAR
ENST00000343470.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LYAR	NM_017816.3 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/10	ENST00000343470.9	NP_060286.1
LYAR	NM_001145725.2 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/10		NP_001139197.1
LYAR	XM_011513505.2 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/10		XP_011511807.1
LYAR	XM_011513506.4 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	3/9		XP_011511808.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LYAR	ENST00000343470.9 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/10	1	NM_017816.3	ENSP00000345917	P1
LYAR	ENST00000452476.5 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/10	1		ENSP00000397367	P1
LYAR	ENST00000513174.1 linkuse as main transcript	c.173A>T	p.Tyr58Phe	missense_variant	4/4	3		ENSP00000420902

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251470

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

203

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.000175

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

May 23, 2023

The c.173A>T (p.Y58F) alteration is located in exon 4 (coding exon 2) of the LYAR gene. This alteration results from a A to T substitution at nucleotide position 173, causing the tyrosine (Y) at amino acid position 58 to be replaced by a phenylalanine (F). 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

Pathogenic

0.73

BayesDel_addAF

Benign

0.0013

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.42

.;.;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

.;.;D

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Uncertain

0.015

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Pathogenic

0.65

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.74

MVP

0.73

MPC

0.30

ClinPred

0.98

GERP RS

2.9

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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