Variant X-121047778-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_012084.4(GLUD2):c.94C>A(p.Arg32=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,172,972 control chromosomes in the GnomAD database, including 47 homozygotes. There are 793 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 31 hom., 415 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 16 hom. 378 hem. )

Consequence

GLUD2
NM_012084.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.116

Variant links:

Genes affected

GLUD2 (HGNC:4336): (glutamate dehydrogenase 2) The protein encoded by this gene is localized to the mitochondrion and acts as a homohexamer to recycle glutamate during neurotransmission. The encoded enzyme catalyzes the reversible oxidative deamination of glutamate to alpha-ketoglutarate. This gene is intronless.[provided by RefSeq, Jan 2010]

GLUD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant X-121047778-C-A is Benign according to our data. Variant chrX-121047778-C-A is described in ClinVar as [Benign]. Clinvar id is 777827.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.116 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.013 (1458/111842) while in subpopulation AFR AF= 0.0448 (1387/30940). AF 95% confidence interval is 0.0429. There are 31 homozygotes in gnomad4. There are 415 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLUD2	NM_012084.4 linkuse as main transcript	c.94C>A	p.Arg32=	synonymous_variant	1/1	ENST00000328078.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLUD2	ENST00000328078.3 linkuse as main transcript	c.94C>A	p.Arg32=	synonymous_variant	1/1		NM_012084.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1442

AN:

111793

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

401

AN XY:

34221

show subpopulations

Gnomad AFR

AF:

0.0444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00531

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:

0.0000189

Gnomad OTH

AF:

0.00858

GnomAD3 exomes

AF:

0.00390

AC:

493

AN:

126315

Hom.:

AF XY:

0.00315

AC XY:

125

AN XY:

39677

show subpopulations

Gnomad AFR exome

AF:

0.0552

Gnomad AMR exome

AF:

0.00264

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000390

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00134

AC:

1420

AN:

1061130

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

378

AN XY:

344064

show subpopulations

Gnomad4 AFR exome

AF:

0.0465

Gnomad4 AMR exome

AF:

0.00264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000160

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000109

Gnomad4 OTH exome

AF:

0.00307

GnomAD4 genome

AF:

0.0130

AC:

1458

AN:

111842

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

415

AN XY:

34280

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.00531

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00846

Alfa

AF:

0.000486

Hom.:

Bravo

AF:

0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

6.3

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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