Variant 4-4274590-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017816.3(LYAR):c.609G>T(p.Lys203Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,613,622 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

LYAR
NM_017816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.046969414).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYAR	NM_017816.3 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	7/10	ENST00000343470.9	NP_060286.1	Q9NX58
LYAR	NM_001145725.2 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	7/10		NP_001139197.1	Q9NX58
LYAR	XM_011513505.2 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	7/10		XP_011511807.1	Q9NX58
LYAR	XM_011513506.4 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	6/9		XP_011511808.1	Q9NX58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYAR	ENST00000343470.9 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	7/10	1	NM_017816.3	ENSP00000345917.4		Q9NX58
LYAR	ENST00000452476.5 linkuse as main transcript	c.609G>T	p.Lys203Asn	missense_variant	7/10	1		ENSP00000397367.1		Q9NX58

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00160

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000774

AC:

194

AN:

250620

Hom.:

AF XY:

0.000760

AC XY:

103

AN XY:

135464

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00140

AC:

2040

AN:

1461340

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

967

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000749

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00161

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152282

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00160

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00149

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000642

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00142

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

Aug 13, 2021

The c.609G>T (p.K203N) alteration is located in exon 7 (coding exon 5) of the LYAR gene. This alteration results from a G to T substitution at nucleotide position 609, causing the lysine (K) at amino acid position 203 to be replaced by an asparagine (N). 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

0.36

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.0073

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.95

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.068

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.11

T;T

Vest4

0.41

MutPred

0.20

Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);

MVP

0.71

MPC

0.17

ClinPred

0.071

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.20

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