2-190880872-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA-CGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant names:

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

Variant summary

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

The NM_014905.5(GLS):​c.-170_-165dupGCAGCA 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 0.036 (139 hom., cov: 0)
  • Exomes 𝑓: 0.055 (2025 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.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.-170_-165dupGCAGCA		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.-170_-165dupGCAGCA		5_prime_UTR_variant	Exon 1 of 18	1	NM_014905.5	ENSP00000317379.3
GLS	ENST00000338435	c.-170_-165dupGCAGCA		5_prime_UTR_variant	Exon 1 of 15	1		ENSP00000340689.4
GLS	ENST00000479552.1	n.44_49dupGCAGCA		non_coding_transcript_exon_variant	Exon 1 of 2	1
ENSG00000235852	ENST00000413911.1	n.838_843dupTGCTGC		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0365 AC: 5452 AN: 149468 Hom.: 139 Cov.: 0

Gnomad AFR AF: 0.0339

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.00663

Gnomad SAS AF: 0.0271

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0283

GnomAD4 exome AF: 0.0548 AC: 32363 AN: 590688 Hom.: 2025 Cov.: 0 AF XY: 0.0531 AC XY: 16729 AN XY: 314760

Gnomad4 AFR exome AF: 0.0478

Gnomad4 AMR exome AF: 0.0263

Gnomad4 ASJ exome AF: 0.0643

Gnomad4 EAS exome AF: 0.00926

Gnomad4 SAS exome AF: 0.0318

Gnomad4 FIN exome AF: 0.0291

Gnomad4 NFE exome AF: 0.0668

Gnomad4 OTH exome AF: 0.0505

GnomAD4 genome AF: 0.0364 AC: 5450 AN: 149568 Hom.: 139 Cov.: 0 AF XY: 0.0352 AC XY: 2565 AN XY: 72894

Gnomad4 AFR AF: 0.0338

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.00645

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0441

Gnomad4 OTH AF: 0.0280

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;