chr12-56474882-C-T

Variant names:

• chr12-56474882-C-T
• rs61731958
• NM_013267.4:c.1011G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_013267.4(GLS2):​c.1011G>A​(p.Gly337Gly) variant causes a synonymous 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. 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 NM_013267.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.681
• Publications: 1 publications found

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]

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

ENSG00000285528 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 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 VariationId is 782561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.681 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.068 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLS2	NM_013267.4	MANE Select	c.1011G>A	p.Gly337Gly	synonymous	Exon 11 of 18	NP_037399.2
	SPRYD4	NM_207344.4	MANE Select	c.*5305C>T		3_prime_UTR	Exon 2 of 2	NP_997227.1	Q8WW59
	GLS2	NM_001280797.2		c.216G>A	p.Gly72Gly	synonymous	Exon 10 of 17	NP_001267726.1	A0A087X004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLS2	ENST00000311966.9	TSL:1 MANE Select	c.1011G>A	p.Gly337Gly	synonymous	Exon 11 of 18	ENSP00000310447.4	Q9UI32-1
	SPRYD4	ENST00000338146.7	TSL:1 MANE Select	c.*5305C>T		3_prime_UTR	Exon 2 of 2	ENSP00000338034.5	Q8WW59
	GLS2	ENST00000424141.6	TSL:1	n.*347G>A		non_coding_transcript_exon	Exon 10 of 17	ENSP00000416282.2	A8K0A6

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3108 AN: 152104 Hom.: 106 Cov.: 32

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

GnomAD2 exomes AF: 0.00542 AC: 1363 AN: 251428 AF XY: 0.00389

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 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.: 32 AF XY: 0.00190 AC XY: 1382 AN XY: 727230

African (AFR) AF: 0.0774 AC: 2591 AN: 33480

American (AMR) AF: 0.00405 AC: 181 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5766

European-Non Finnish (NFE) AF: 0.0000944 AC: 105 AN: 1112000

Other (OTH) AF: 0.00515 AC: 311 AN: 60396

GnomAD4 genome AF: 0.0205 AC: 3118 AN: 152222 Hom.: 107 Cov.: 32 AF XY: 0.0191 AC XY: 1420 AN XY: 74426

African (AFR) AF: 0.0701 AC: 2911 AN: 41506

American (AMR) AF: 0.0110 AC: 168 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68002

Other (OTH) AF: 0.0133 AC: 28 AN: 2110

Alfa AF: 0.00958 Hom.: 34

Bravo AF: 0.0241

ESP6500AA AF: 0.0649 AC: 286

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00651 AC: 790

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	4.3
DANN	Benign	0.76
DEOGEN2	Benign	0.0065	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0018	T
PhyloP100		-0.68
Vest4		0.19
MVP		0.48
GERP RS		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61731958; hg19: chr12-56868666;