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Variant names:

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

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_014905.5(GLS):​c.-167_-165delGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 729,186 control chromosomes in the GnomAD database, including 8,550 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2959 hom., cov: 0)
  • Exomes 𝑓: 0.20 (5591 hom.)
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.606

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.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-167_-165delGCA		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_-165delGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435	c.-167_-165delGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.47_49delGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.841_843delTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28557 AN: 149278 Hom.: 2957 Cov.: 0

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0856

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.202 AC: 117007 AN: 579810 Hom.: 5591 AF XY: 0.205 AC XY: 63201 AN XY: 308624

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.0999

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.191 AC: 28570 AN: 149376 Hom.: 2959 Cov.: 0 AF XY: 0.193 AC XY: 14034 AN XY: 72808

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;