2-190880872-CGCAGCAGCAGCAGCA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014905.5(GLS):c.-179_-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 0.0085 in 742,618 control chromosomes in the GnomAD database, including 158 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (56 hom., cov: 0)
  • Exomes 𝑓: 0.0063 (102 hom.)
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter 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 -10 ACMG points.

• BP6: Variant 2-190880872-CGCAGCAGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3054764.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2575/149606) while in subpopulation AFR AF= 0.0416 (1695/40698). AF 95% confidence interval is 0.04. There are 56 homozygotes in gnomad4. There are 1245 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 56 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-179_-165del		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.758_772del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-179_-165del		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-179_-165del		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.829_843del		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.35_49del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2564 AN: 149506 Hom.: 56 Cov.: 0

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.00554

Gnomad AMR AF: 0.00967

Gnomad ASJ AF: 0.00986

Gnomad EAS AF: 0.00744

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00672

Gnomad OTH AF: 0.0137

GnomAD4 exome AF: 0.00630 AC: 3734 AN: 593012 Hom.: 102 AF XY: 0.00627 AC XY: 1980 AN XY: 315982

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.00807

Gnomad4 ASJ exome AF: 0.00825

Gnomad4 EAS exome AF: 0.00535

Gnomad4 SAS exome AF: 0.00527

Gnomad4 FIN exome AF: 0.0144

Gnomad4 NFE exome AF: 0.00444

Gnomad4 OTH exome AF: 0.00771

GnomAD4 genome AF: 0.0172 AC: 2575 AN: 149606 Hom.: 56 Cov.: 0 AF XY: 0.0171 AC XY: 1245 AN XY: 72924

Gnomad4 AFR AF: 0.0416

Gnomad4 AMR AF: 0.00966

Gnomad4 ASJ AF: 0.00986

Gnomad4 EAS AF: 0.00746

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.00674

Gnomad4 OTH AF: 0.0140

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

Apr 15, 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;