chr2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-C

Position:

• chr2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS1

The NM_014905.5(GLS):​c.-191_-165del 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 0.00078 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (5 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: 0.335

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3358513.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000782 (117/149574) while in subpopulation AFR AF= 0.00147 (60/40696). AF 95% confidence interval is 0.00117. There are 0 homozygotes in gnomad4. There are 55 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.-191_-165del		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.746_772del		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-191_-165del		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-191_-165del		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.817_843del		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.23_49del		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.000783 AC: 117 AN: 149474 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000402

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000982

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000550

Gnomad OTH AF: 0.000488

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00197 AC: 1153 AN: 586256 Hom.: 5 AF XY: 0.00192 AC XY: 600 AN XY: 312350

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00100

Gnomad4 ASJ exome AF: 0.00156

Gnomad4 EAS exome AF: 0.00388

Gnomad4 SAS exome AF: 0.000634

Gnomad4 FIN exome AF: 0.00259

Gnomad4 NFE exome AF: 0.00208

Gnomad4 OTH exome AF: 0.00240

GnomAD4 genome AF: 0.000782 AC: 117 AN: 149574 Hom.: 0 Cov.: 0 AF XY: 0.000754 AC XY: 55 AN XY: 72908

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000403

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000982

Gnomad4 NFE AF: 0.000550

Gnomad4 OTH AF: 0.000483

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

Sep 19, 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;