2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCA

Variant names:

• chr2-190880872-CGCAGCAGCAGCAGCAGCA-C
• rs57674096
• NM_014905.5:c.-182_-165delGCAGCAGCAGCAGCAGCA

Variant summary

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

The NM_014905.5(GLS):​c.-182_-165delGCAGCAGCAGCAGCAGCA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 740,778 control chromosomes in the GnomAD database, including 820 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.046 (322 hom., cov: 0)
  • Exomes 𝑓: 0.017 (498 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 (AMR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-182_-165delGCAGCAGCAGCAGCAGCA		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.-182_-165delGCAGCAGCAGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435	c.-182_-165delGCAGCAGCAGCAGCAGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.32_49delGCAGCAGCAGCAGCAGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.826_843delTGCTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6883 AN: 149480 Hom.: 319 Cov.: 0

Gnomad AFR AF: 0.0986

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0125

Gnomad EAS AF: 0.00704

Gnomad SAS AF: 0.0325

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0400

GnomAD4 exome AF: 0.0167 AC: 9857 AN: 591198 Hom.: 498 AF XY: 0.0163 AC XY: 5129 AN XY: 314958

Gnomad4 AFR exome AF: 0.0639

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.00506

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.00902

Gnomad4 NFE exome AF: 0.00798

Gnomad4 OTH exome AF: 0.0203

GnomAD4 genome AF: 0.0461 AC: 6899 AN: 149580 Hom.: 322 Cov.: 0 AF XY: 0.0467 AC XY: 3405 AN XY: 72912

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.0125

Gnomad4 EAS AF: 0.00685

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0174

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0396

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;