chr2-190880872-C-CGCAGCAGCAGCAGCAGCA

Position:

• chr2-190880872-C-CGCAGCAGCAGCAGCAGCA

Variant summary

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

The NM_014905.5(GLS):​c.-182_-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 0.0032 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0054 (456 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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 2-190880872-C-CGCAGCAGCAGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCAGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3352614.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00317 (475/149608) while in subpopulation AFR AF= 0.00381 (155/40700). AF 95% confidence interval is 0.00332. There are 0 homozygotes in gnomad4. There are 243 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.-182_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-182_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-182_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.32_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.00318 AC: 475 AN: 149508 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00378

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.000402

Gnomad SAS AF: 0.00256

Gnomad FIN AF: 0.00118

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00330

Gnomad OTH AF: 0.00293

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00541 AC: 3212 AN: 593378 Hom.: 456 Cov.: 0 AF XY: 0.00531 AC XY: 1679 AN XY: 316164

Gnomad4 AFR exome AF: 0.00692

Gnomad4 AMR exome AF: 0.00453

Gnomad4 ASJ exome AF: 0.00324

Gnomad4 EAS exome AF: 0.00159

Gnomad4 SAS exome AF: 0.00419

Gnomad4 FIN exome AF: 0.00140

Gnomad4 NFE exome AF: 0.00632

Gnomad4 OTH exome AF: 0.00557

GnomAD4 genome AF: 0.00317 AC: 475 AN: 149608 Hom.: 0 Cov.: 0 AF XY: 0.00333 AC XY: 243 AN XY: 72926

Gnomad4 AFR AF: 0.00381

Gnomad4 AMR AF: 0.00377

Gnomad4 ASJ AF: 0.00232

Gnomad4 EAS AF: 0.000403

Gnomad4 SAS AF: 0.00235

Gnomad4 FIN AF: 0.00118

Gnomad4 NFE AF: 0.00330

Gnomad4 OTH AF: 0.00290

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

May 09, 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;