Variant chrX-48761797-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001080489.3(GLOD5):c.7C>T(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000756 in 1,163,875 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000078 ( 0 hom. 31 hem. )

Consequence

GLOD5
NM_001080489.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.888

Variant links:

Genes affected

GLOD5 (HGNC:33358): (glyoxalase domain containing 5) This gene encodes a protein with a glyoxalase domain. [provided by RefSeq, Sep 2011]

GLOD5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012768865).

BP6

Variant X-48761797-C-T is Benign according to our data. Variant chrX-48761797-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2458939.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLOD5	NM_001080489.3 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	1/4	ENST00000303227.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLOD5	ENST00000303227.11 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	1/4	5	NM_001080489.3	P1
GLOD5	ENST00000463327.1 linkuse as main transcript	n.47C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000538

AC:

AN:

111490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33656

show subpopulations

Gnomad AFR

AF:

0.0000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000851

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000186

AC:

AN:

112892

Hom.:

AF XY:

0.000246

AC XY:

AN XY:

40568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00221

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000686

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000779

AC:

AN:

1052385

Hom.:

Cov.:

AF XY:

0.0000903

AC XY:

AN XY:

343257

show subpopulations

Gnomad4 AFR exome

AF:

0.0000402

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000537

Gnomad4 EAS exome

AF:

0.000737

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000697

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000538

AC:

AN:

111490

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33656

show subpopulations

Gnomad4 AFR

AF:

0.0000652

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000851

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000841

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.2

DANN

Benign

0.82

DEOGEN2

Benign

0.027

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.55

M_CAP

Benign

0.0028

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.75

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.050

REVEL

Benign

0.036

Sift

Benign

0.057

Sift4G

Benign

0.18

Vest4

0.11

MutPred

0.27

Gain of catalytic residue at M1 (P = 0);

MVP

0.10

MPC

0.011

ClinPred

0.031

GERP RS

-7.9

Varity_R

0.045

gMVP

0.23

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