2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr2-190880872-CGCAGCAGCAGCA-C
• rs57674096
• NM_014905.5:c.-176_-165delGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_014905.5(GLS):​c.-176_-165delGCAGCAGCAGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00461 in 742,372 control chromosomes in the GnomAD database, including 96 homozygotes. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.011 (33 hom., cov: 0)
  • Exomes 𝑓: 0.0029 (63 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]

ENSG00000235852 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 2-190880872-CGCAGCAGCAGCA-C is Benign according to our data. Variant chr2-190880872-CGCAGCAGCAGCA-C is described in ClinVar as [Likely_benign]. Clinvar id is 3047867.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0114 (1700/149600) while in subpopulation AFR AF= 0.0358 (1456/40692). AF 95% confidence interval is 0.0343. There are 33 homozygotes in gnomad4. There are 795 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-176_-165delGCAGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 18	ENST00000320717.8	NP_055720.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLS	ENST00000320717	c.-176_-165delGCAGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435	c.-176_-165delGCAGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.38_49delGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.832_843delTGCTGCTGCTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1692 AN: 149500 Hom.: 34 Cov.: 0

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00345

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.00299

Gnomad FIN AF: 0.000294

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00187

Gnomad OTH AF: 0.0122

GnomAD4 exome AF: 0.00290 AC: 1720 AN: 592772 Hom.: 63 AF XY: 0.00271 AC XY: 855 AN XY: 315810

Gnomad4 AFR exome AF: 0.0349

Gnomad4 AMR exome AF: 0.00319

Gnomad4 ASJ exome AF: 0.000455

Gnomad4 EAS exome AF: 0.00381

Gnomad4 SAS exome AF: 0.00326

Gnomad4 FIN exome AF: 0.0000318

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.00538

GnomAD4 genome AF: 0.0114 AC: 1700 AN: 149600 Hom.: 33 Cov.: 0 AF XY: 0.0109 AC XY: 795 AN XY: 72926

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00344

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.00299

Gnomad4 FIN AF: 0.000294

Gnomad4 NFE AF: 0.00187

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

Sep 30, 2021

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;