Variant 4-4274649-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017816.3(LYAR):c.550G>T(p.Val184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LYAR
NM_017816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.153

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044340074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYAR	NM_017816.3 link	c.550G>T	p.Val184Leu	missense_variant	7/10	ENST00000343470.9	NP_060286.1	Q9NX58
LYAR	NM_001145725.2 link	c.550G>T	p.Val184Leu	missense_variant	7/10		NP_001139197.1	Q9NX58
LYAR	XM_011513505.2 link	c.550G>T	p.Val184Leu	missense_variant	7/10		XP_011511807.1	Q9NX58
LYAR	XM_011513506.4 link	c.550G>T	p.Val184Leu	missense_variant	6/9		XP_011511808.1	Q9NX58

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYAR	ENST00000343470.9 link	c.550G>T	p.Val184Leu	missense_variant	7/10	1	NM_017816.3	ENSP00000345917.4		Q9NX58
LYAR	ENST00000452476.5 link	c.550G>T	p.Val184Leu	missense_variant	7/10	1		ENSP00000397367.1		Q9NX58

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

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:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Dec 21, 2023

The c.550G>T (p.V184L) 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 550, causing the valine (V) at amino acid position 184 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

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

4.0

DANN

Benign

0.84

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.25

M_CAP

Benign

0.0062

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.050

Sift

Benign

0.53

T;T

Sift4G

Benign

0.33

T;T

Vest4

0.077

MutPred

0.10

Loss of ubiquitination at K186 (P = 0.1055);Loss of ubiquitination at K186 (P = 0.1055);

MVP

0.27

MPC

0.062

ClinPred

0.067

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.093

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