2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr2-190880872-CGCAGCA-C
• rs57674096
• NM_014905.5:c.-170_-165delGCAGCA

Variant summary

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

The NM_014905.5(GLS):​c.-170_-165delGCAGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 710,966 control chromosomes in the GnomAD database, including 5,971 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1869 hom., cov: 0)
  • Exomes 𝑓: 0.14 (4102 hom.)
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-170_-165delGCAGCA		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	ENST00000320717.8	c.-170_-165delGCAGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435.9	c.-170_-165delGCAGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.44_49delGCAGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.838_843delTGCTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 21801 AN: 149318 Hom.: 1870 Cov.: 0

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.0610

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.0542

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.145 AC: 81317 AN: 561550 Hom.: 4102 AF XY: 0.151 AC XY: 44902 AN XY: 298000

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.315

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.0816

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.146 AC: 21823 AN: 149416 Hom.: 1869 Cov.: 0 AF XY: 0.146 AC XY: 10650 AN XY: 72836

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0542

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.154

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;