Variant chr12-56474882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000539272.5(GLS2):c.833G>A(p.Gly278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,614,078 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 107 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 105 hom. )

Consequence

GLS2
ENST00000539272.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.681

Variant links:

Genes affected

GLS2 (HGNC:29570): (glutaminase 2) The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

GLS2 links:

SPRYD4 (HGNC:27468): (SPRY domain containing 4) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SPRYD4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018049479).

BP6

Variant 12-56474882-C-T is Benign according to our data. Variant chr12-56474882-C-T is described in ClinVar as [Benign]. Clinvar id is 782561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS2	NM_013267.4 linkuse as main transcript	c.1011G>A	p.Gly337=	synonymous_variant	11/18	ENST00000311966.9
SPRYD4	NM_207344.4 linkuse as main transcript	c.*5305C>T		3_prime_UTR_variant	2/2	ENST00000338146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS2	ENST00000311966.9 linkuse as main transcript	c.1011G>A	p.Gly337=	synonymous_variant	11/18	1	NM_013267.4	P1	Q9UI32-1
SPRYD4	ENST00000338146.7 linkuse as main transcript	c.*5305C>T		3_prime_UTR_variant	2/2	1	NM_207344.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0204

AC:

3108

AN:

152104

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0110

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00542

AC:

1363

AN:

251428

Hom.:

AF XY:

0.00389

AC XY:

528

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00220

AC:

3219

AN:

1461856

Hom.:

105

Cov.:

AF XY:

0.00190

AC XY:

1382

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0774

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000944

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.0205

AC:

3118

AN:

152222

Hom.:

107

Cov.:

AF XY:

0.0191

AC XY:

1420

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0701

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00946

Hom.:

Bravo

AF:

0.0241

ESP6500AA

AF:

0.0649

AC:

286

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00651

AC:

790

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.3

DANN

Benign

0.76

DEOGEN2

Benign

0.0065

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0018

MutationTaster

Benign

1.0

Vest4

0.19

MVP

0.48

GERP RS

-1.3

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