Variant chrX-48765878-G-A 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.107G>A(p.Arg36His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000092 in 1,195,916 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 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 0.00014 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000087 ( 0 hom. 31 hem. )

Consequence

GLOD5
NM_001080489.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0820

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=0.045315593).

BP6

Variant X-48765878-G-A is Benign according to our data. Variant chrX-48765878-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2355296.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLOD5	NM_001080489.3 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	2/4	ENST00000303227.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GLOD5	ENST00000303227.11 linkuse as main transcript	c.107G>A	p.Arg36His	missense_variant	2/4	5	NM_001080489.3	P1
GLOD5	ENST00000445229.1 linkuse as main transcript	c.8G>A	p.Arg3His	missense_variant	1/3	2
GLOD5	ENST00000463327.1 linkuse as main transcript	n.147G>A		non_coding_transcript_exon_variant	2/2	2
GLOD5	ENST00000470676.1 linkuse as main transcript	n.100G>A		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

110784

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

33030

show subpopulations

Gnomad AFR

AF:

0.0000658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000194

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.000377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000170

Gnomad OTH

AF:

0.000671

GnomAD3 exomes

AF:

0.0000374

AC:

AN:

160572

Hom.:

AF XY:

0.0000610

AC XY:

AN XY:

49144

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000844

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000866

AC:

AN:

1085132

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

352322

show subpopulations

Gnomad4 AFR exome

AF:

0.0000383

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000999

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000899

Gnomad4 OTH exome

AF:

0.000329

GnomAD4 genome

AF:

0.000144

AC:

AN:

110784

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

33030

show subpopulations

Gnomad4 AFR

AF:

0.0000658

Gnomad4 AMR

AF:

0.000194

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000170

Gnomad4 OTH

AF:

0.000671

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.0000982

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000309

AC:

ExAC

AF:

0.00000828

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

Nov 09, 2021

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

0.082

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.23

DANN

Benign

0.93

DEOGEN2

Benign

0.035

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.26

M_CAP

Benign

0.0012

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.060

REVEL

Benign

0.054

Sift

Benign

0.27

Sift4G

Benign

0.26

Vest4

0.066

MVP

0.56

MPC

0.011

ClinPred

0.030

GERP RS

-1.5

Varity_R

0.15

gMVP

0.18

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