2-190880872-C-CGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_014905.5(GLS):c.-188_-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 (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0012 (9 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter 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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-190880872-C-CGCAGCAGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCAGCAGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3054076.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00142 (213/149612) while in subpopulation AFR AF= 0.00162 (66/40702). AF 95% confidence interval is 0.00137. There are 1 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-188_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-188_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-188_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.26_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 213 AN: 149512 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00139

Gnomad ASJ AF: 0.000870

Gnomad EAS AF: 0.000603

Gnomad SAS AF: 0.000854

Gnomad FIN AF: 0.0000981

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00244

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00120 AC: 714 AN: 593510 Hom.: 9 Cov.: 0 AF XY: 0.00126 AC XY: 397 AN XY: 316232

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.000804

Gnomad4 ASJ exome AF: 0.000909

Gnomad4 EAS exome AF: 0.000578

Gnomad4 SAS exome AF: 0.00100

Gnomad4 FIN exome AF: 0.000446

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00142 AC: 213 AN: 149612 Hom.: 1 Cov.: 0 AF XY: 0.00140 AC XY: 102 AN XY: 72928

Gnomad4 AFR AF: 0.00162

Gnomad4 AMR AF: 0.00139

Gnomad4 ASJ AF: 0.000870

Gnomad4 EAS AF: 0.000605

Gnomad4 SAS AF: 0.000855

Gnomad4 FIN AF: 0.0000981

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.00242

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

GLS-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 01, 2021

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;