Variant rs369808296 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032569.4(GLYR1):c.596C>T(p.Ala199Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

GLYR1
NM_032569.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.87

Variant links:

Genes affected

GLYR1 (HGNC:24434): (glyoxylate reductase 1 homolog) Enables DNA binding activity; methylated histone binding activity; and nucleosome binding activity. Involved in positive regulation of histone acetylation and positive regulation of transcription by RNA polymerase II. Located in cytosol and nucleoplasm. Part of nucleosome. [provided by Alliance of Genome Resources, Apr 2022]

GLYR1 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=0.11036211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLYR1	NM_032569.4 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/16	ENST00000321919.14	NP_115958.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLYR1	ENST00000321919.14 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/16	1	NM_032569.4	ENSP00000322716	P1	Q49A26-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251476

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

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:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151778

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74068

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GLYR1-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Undiagnosed Diseases Network, NIH

Mar 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

.;T;.;T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.94

D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

.;N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.54

N;N;.;.;.

REVEL

Benign

0.092

Sift

Benign

0.34

T;D;.;.;.

Sift4G

Benign

0.70

T;T;T;.;T

Polyphen

0.21

B;B;B;.;.

Vest4

0.33

MVP

0.35

MPC

0.020

ClinPred

0.12

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.30

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