2-190880872-C-CGCAGCAGCAGCAGCA

Position:

• chr2-190880872-C-CGCAGCAGCAGCAGCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014905.5(GLS):​c.-179_-165dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (6 hom., cov: 0)
  • Exomes 𝑓: 0.0083 (628 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLS NM_014905.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-190880872-C-CGCAGCAGCAGCAGCA is Benign according to our data. Variant chr2-190880872-C-CGCAGCAGCAGCAGCA is described in ClinVar as [Benign]. Clinvar id is 1879513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00568 (850/149608) while in subpopulation AMR AF= 0.0108 (163/15112). AF 95% confidence interval is 0.00943. There are 6 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLS	NM_014905.5	c.-179_-165dup		5_prime_UTR_variant	1/18	ENST00000320717.8
LOC124906110	XR_007087791.1	n.772_773insTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLS	ENST00000320717.8	c.-179_-165dup		5_prime_UTR_variant	1/18	1	NM_014905.5	P1
GLS	ENST00000338435.9	c.-179_-165dup		5_prime_UTR_variant	1/15	1
	ENST00000413911.1	n.843_844insTGCTGCTGCTGCTGC		non_coding_transcript_exon_variant	2/2	3
GLS	ENST00000479552.1	n.35_49dup		non_coding_transcript_exon_variant	1/2	1

Frequencies

GnomAD3 genomes AF: 0.00567 AC: 848 AN: 149508 Hom.: 6 Cov.: 0

Gnomad AFR AF: 0.00646

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00201

Gnomad SAS AF: 0.00320

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00532

Gnomad OTH AF: 0.00586

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00833 AC: 4945 AN: 593342 Hom.: 628 Cov.: 0 AF XY: 0.00808 AC XY: 2554 AN XY: 316130

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.00736

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00108

Gnomad4 SAS exome AF: 0.00556

Gnomad4 FIN exome AF: 0.00321

Gnomad4 NFE exome AF: 0.00998

Gnomad4 OTH exome AF: 0.00876

GnomAD4 genome AF: 0.00568 AC: 850 AN: 149608 Hom.: 6 Cov.: 0 AF XY: 0.00590 AC XY: 430 AN XY: 72928

Gnomad4 AFR AF: 0.00649

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.000290

Gnomad4 EAS AF: 0.00202

Gnomad4 SAS AF: 0.00321

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00532

Gnomad4 OTH AF: 0.00580

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

GLS: BS1, BS2 -

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;