2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr2-190880872-C-CGCA
• rs57674096
• NM_014905.5:c.-167_-165dupGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014905.5(GLS):​c.-167_-165dupGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.038 (122 hom., cov: 0)
  • Exomes 𝑓: 0.046 (419 hom.)
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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]

ENSG00000235852 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0376 (5617/149548) while in subpopulation NFE AF= 0.0418 (2811/67222). AF 95% confidence interval is 0.0405. There are 122 homozygotes in gnomad4. There are 2829 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 122 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-167_-165dupGCA		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.-167_-165dupGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435	c.-167_-165dupGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.47_49dupGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.841_843dupTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0376 AC: 5613 AN: 149448 Hom.: 122 Cov.: 0

Gnomad AFR AF: 0.0255

Gnomad AMI AF: 0.0255

Gnomad AMR AF: 0.0323

Gnomad ASJ AF: 0.0348

Gnomad EAS AF: 0.0165

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0401

GnomAD4 exome AF: 0.0457 AC: 26855 AN: 587410 Hom.: 419 Cov.: 0 AF XY: 0.0450 AC XY: 14090 AN XY: 312942

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.0274

Gnomad4 ASJ exome AF: 0.0455

Gnomad4 EAS exome AF: 0.0176

Gnomad4 SAS exome AF: 0.0374

Gnomad4 FIN exome AF: 0.0721

Gnomad4 NFE exome AF: 0.0491

Gnomad4 OTH exome AF: 0.0450

GnomAD4 genome AF: 0.0376 AC: 5617 AN: 149548 Hom.: 122 Cov.: 0 AF XY: 0.0388 AC XY: 2829 AN XY: 72898

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0348

Gnomad4 EAS AF: 0.0167

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0397

ClinVar

Not reported in ClinVar

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;