2-190880872-CGCAGCAGCA-C

Variant names:

• chr2-190880872-CGCAGCAGCA-C
• rs57674096
• NM_014905.5:c.-173_-165delGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_014905.5(GLS):​c.-173_-165delGCAGCAGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 728,690 control chromosomes in the GnomAD database, including 448 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.029 (168 hom., cov: 0)
  • Exomes 𝑓: 0.018 (280 hom.)
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.335

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]

ENSG00000235852 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 2-190880872-CGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3047628.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-173_-165delGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 18	ENST00000320717.8	NP_055720.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLS	ENST00000320717	c.-173_-165delGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3

Frequencies

GnomAD3 genomes AF: 0.0293 AC: 4383 AN: 149456 Hom.: 167 Cov.: 0

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00957

Gnomad EAS AF: 0.0374

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.000196

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.0269

GnomAD4 exome AF: 0.0177 AC: 10238 AN: 579134 Hom.: 280 AF XY: 0.0187 AC XY: 5760 AN XY: 307724

Gnomad4 AFR exome AF: 0.0938

Gnomad4 AMR exome AF: 0.0287

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.0551

Gnomad4 SAS exome AF: 0.0442

Gnomad4 FIN exome AF: 0.00240

Gnomad4 NFE exome AF: 0.00782

Gnomad4 OTH exome AF: 0.0212

GnomAD4 genome AF: 0.0293 AC: 4389 AN: 149556 Hom.: 168 Cov.: 0 AF XY: 0.0285 AC XY: 2075 AN XY: 72900

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.00957

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.0331

Gnomad4 FIN AF: 0.000196

Gnomad4 NFE AF: 0.00573

Gnomad4 OTH AF: 0.0266

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLS-related disorder Benign:1

Sep 27, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs57674096; hg19: chr2-191745598;