2-190880872-C-CGCAGCAGCAGCA

Position:

• chr2-190880872-C-CGCAGCAGCAGCA

Variant summary

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

The NM_014905.5(GLS):​c.-176_-165dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.012 (19 hom., cov: 0)
  • Exomes 𝑓: 0.017 (1020 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.922

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-C-CGCAGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3353203.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0118 (1771/149588) while in subpopulation AMR AF= 0.0164 (248/15108). AF 95% confidence interval is 0.0147. There are 19 homozygotes in gnomad4. There are 838 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 19 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-176_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-176_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-176_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.38_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.0119 AC: 1773 AN: 149488 Hom.: 19 Cov.: 0

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00222

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00696

Gnomad EAS AF: 0.00241

Gnomad SAS AF: 0.00875

Gnomad FIN AF: 0.00902

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0161

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0174 AC: 10337 AN: 593034 Hom.: 1020 Cov.: 0 AF XY: 0.0169 AC XY: 5328 AN XY: 315940

Gnomad4 AFR exome AF: 0.0173

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00580

Gnomad4 EAS exome AF: 0.00173

Gnomad4 SAS exome AF: 0.0112

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.0212

Gnomad4 OTH exome AF: 0.0156

GnomAD4 genome AF: 0.0118 AC: 1771 AN: 149588 Hom.: 19 Cov.: 0 AF XY: 0.0115 AC XY: 838 AN XY: 72920

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.00696

Gnomad4 EAS AF: 0.00242

Gnomad4 SAS AF: 0.00855

Gnomad4 FIN AF: 0.00902

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0159

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

Jun 03, 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;