Genetic Variant NM_013267.4:c.1258G>A (chr12-56473561-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_013267.4(GLS2):c.1258G>A(p.Ala420Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GLS2
NM_013267.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91

Publications

0 publications found

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:

ENSG00000285528 (HGNC:):

ENSG00000285528 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013267.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLS2	NM_013267.4	MANE Select	c.1258G>A	p.Ala420Thr	missense	Exon 13 of 18	NP_037399.2
SPRYD4	NM_207344.4	MANE Select	c.*3984C>T		3_prime_UTR	Exon 2 of 2	NP_997227.1	Q8WW59
GLS2	NM_001280797.2		c.463G>A	p.Ala155Thr	missense	Exon 12 of 17	NP_001267726.1	A0A087X004

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GLS2	ENST00000311966.9	TSL:1 MANE Select	c.1258G>A	p.Ala420Thr	missense	Exon 13 of 18	ENSP00000310447.4	Q9UI32-1
SPRYD4	ENST00000338146.7	TSL:1 MANE Select	c.*3984C>T		3_prime_UTR	Exon 2 of 2	ENSP00000338034.5	Q8WW59
GLS2	ENST00000424141.6	TSL:1	n.*594G>A		non_coding_transcript_exon	Exon 12 of 17	ENSP00000416282.2	A8K0A6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460532

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726532

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4828

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111870

Other (OTH)

AF:

0.00

AC:

AN:

60292

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.0025

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.51

MutationAssessor

Pathogenic

3.0

PhyloP100

7.9

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.32

Sift

Benign

0.054

Sift4G

Uncertain

0.014

Polyphen

0.92

Vest4

0.68

MutPred

0.73

Gain of catalytic residue at V425 (P = 0)

MVP

0.79

MPC

0.84

ClinPred

0.97

GERP RS

5.1

Varity_R

0.48

gMVP

0.89

Mutation Taster

=57/43

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over