chr2-190880872-CGCAGCAGCAGCAGCAGCAGCA-C

Position:

• chr2-190880872-CGCAGCAGCAGCAGCAGCAGCA-C

Variant summary

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

The NM_014905.5(GLS):​c.-185_-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 0.00971 in 741,078 control chromosomes in the GnomAD database, including 161 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.014 (37 hom., cov: 0)
  • Exomes 𝑓: 0.0087 (124 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-CGCAGCAGCAGCAGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCAGCAGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3032445.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-185_-165del		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.752_772del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-185_-165del		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-185_-165del		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.823_843del		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.29_49del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2030 AN: 149508 Hom.: 37 Cov.: 0

Gnomad AFR AF: 0.00638

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.000580

Gnomad EAS AF: 0.0607

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00891

Gnomad OTH AF: 0.0122

GnomAD4 exome AF: 0.00874 AC: 5168 AN: 591470 Hom.: 124 AF XY: 0.00883 AC XY: 2780 AN XY: 315002

Gnomad4 AFR exome AF: 0.00436

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.000511

Gnomad4 EAS exome AF: 0.0459

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.00546

Gnomad4 OTH exome AF: 0.00800

GnomAD4 genome AF: 0.0136 AC: 2028 AN: 149608 Hom.: 37 Cov.: 0 AF XY: 0.0151 AC XY: 1099 AN XY: 72924

Gnomad4 AFR AF: 0.00636

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.000580

Gnomad4 EAS AF: 0.0607

Gnomad4 SAS AF: 0.0314

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.00891

Gnomad4 OTH AF: 0.0121

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

Nov 17, 2022

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;