Genetic Variant ENST00000390288.6:n.1072C>G (chr12-56471272-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000390288.6(GLS2):n.1072C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 533,762 control chromosomes in the GnomAD database, including 8,150 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2053 hom., cov: 32)

Exomes 𝑓: 0.17 ( 6097 hom. )

Consequence

GLS2
ENST00000390288.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

37 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS2	NM_013267.4 link	c.*215C>G		3_prime_UTR_variant	Exon 18 of 18	ENST00000311966.9	NP_037399.2	Q9UI32-1
SPRYD4	NM_207344.4 link	c.*1695G>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000338146.7	NP_997227.1	Q8WW59

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GLS2	ENST00000311966.9 link	c.*215C>G	3_prime_UTR_variant	Exon 18 of 18	1	NM_013267.4	ENSP00000310447.4	Q9UI32-1
SPRYD4	ENST00000338146.7 link	c.*1695G>C	3_prime_UTR_variant	Exon 2 of 2	1	NM_207344.4	ENSP00000338034.5	Q8WW59
ENSG00000285528	ENST00000648304.1 link	n.182+16665C>G	intron_variant	Intron 1 of 3			ENSP00000497190.1	A0A3B3IS89

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23241

AN:

152102

Hom.:

2046

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0898

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.172

AC:

65706

AN:

381544

Hom.:

6097

Cov.:

AF XY:

0.173

AC XY:

34040

AN XY:

197316

show subpopulations

African (AFR)

AF:

0.0707

AC:

787

AN:

11128

American (AMR)

AF:

0.211

AC:

2887

AN:

13710

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

2381

AN:

12296

East Asian (EAS)

AF:

0.103

AC:

2934

AN:

28590

South Asian (SAS)

AF:

0.138

AC:

3600

AN:

26012

European-Finnish (FIN)

AF:

0.179

AC:

4826

AN:

26904

Middle Eastern (MID)

AF:

0.221

AC:

392

AN:

1772

European-Non Finnish (NFE)

AF:

0.185

AC:

44029

AN:

238158

Other (OTH)

AF:

0.168

AC:

3870

AN:

22974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

2839

5679

8518

11358

14197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

302

604

906

1208

1510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.153

AC:

23260

AN:

152218

Hom.:

2053

Cov.:

AF XY:

0.154

AC XY:

11472

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0712

AC:

2960

AN:

41570

American (AMR)

AF:

0.207

AC:

3156

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

645

AN:

3470

East Asian (EAS)

AF:

0.0891

AC:

460

AN:

5162

South Asian (SAS)

AF:

0.148

AC:

715

AN:

4828

European-Finnish (FIN)

AF:

0.186

AC:

1971

AN:

10586

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12646

AN:

68002

Other (OTH)

AF:

0.168

AC:

355

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

992

1983

2975

3966

4958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.181

Hom.:

1443

Bravo

AF:

0.150

Asia WGS

AF:

0.141

AC:

492

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.69

PhyloP100

-0.20

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over