2-190905887-T-G

Position:

• chr2-190905887-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014905.5(GLS):​c.979+720T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,038 control chromosomes in the GnomAD database, including 1,907 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 0.14 (1907 hom., cov: 32)
• Consequence: GLS NM_014905.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

GLS (HGNC:4331): (glutaminase) This gene encodes the K-type mitochondrial glutaminase. The encoded protein is an phosphate-activated amidohydrolase that catalyzes the hydrolysis of glutamine to glutamate and ammonia. This protein is primarily expressed in the brain and kidney plays an essential role in generating energy for metabolism, synthesizing the brain neurotransmitter glutamate and maintaining acid-base balance in the kidney. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

GLS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLS	NM_014905.5	c.979+720T>G		intron_variant		ENST00000320717.8	NP_055720.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLS	ENST00000320717.8	c.979+720T>G		intron_variant		1	NM_014905.5	ENSP00000317379.3

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20698 AN: 151920 Hom.: 1898 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0484

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20729 AN: 152038 Hom.: 1907 Cov.: 32 AF XY: 0.139 AC XY: 10311 AN XY: 74294

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.143

Alfa AF: 0.110 Hom.: 677

Bravo AF: 0.157

Asia WGS AF: 0.233 AC: 811 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs3771311; hg19: chr2-191770613;