2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-C

Position:

• chr2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_014905.5(GLS):​c.-194_-165del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 742,982 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00095 (4 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3031213.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00234 (350/149612) while in subpopulation AFR AF= 0.00287 (117/40702). AF 95% confidence interval is 0.00245. There are 1 homozygotes in gnomad4. There are 179 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-194_-165del		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.743_772del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-194_-165del		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-194_-165del		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.814_843del		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.20_49del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 350 AN: 149512 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000795

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00261

Gnomad SAS AF: 0.000427

Gnomad FIN AF: 0.00186

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00146

GnomAD4 exome AF: 0.000954 AC: 566 AN: 593370 Hom.: 4 AF XY: 0.000854 AC XY: 270 AN XY: 316170

Gnomad4 AFR exome AF: 0.00132

Gnomad4 AMR exome AF: 0.000418

Gnomad4 ASJ exome AF: 0.000170

Gnomad4 EAS exome AF: 0.000542

Gnomad4 SAS exome AF: 0.0000646

Gnomad4 FIN exome AF: 0.00162

Gnomad4 NFE exome AF: 0.00116

Gnomad4 OTH exome AF: 0.000626

GnomAD4 genome AF: 0.00234 AC: 350 AN: 149612 Hom.: 1 Cov.: 0 AF XY: 0.00245 AC XY: 179 AN XY: 72928

Gnomad4 AFR AF: 0.00287

Gnomad4 AMR AF: 0.000794

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00262

Gnomad4 SAS AF: 0.000428

Gnomad4 FIN AF: 0.00186

Gnomad4 NFE AF: 0.00271

Gnomad4 OTH AF: 0.00145

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

GLS-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 14, 2024

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;