rs3217036

Variant names:

• chr2-190894951-AT-A
• rs3217036
• NM_014905.5:c.387-193delT

Your query was ambiguous. Multiple possible variants found:

• chr2-190894951-AT-A
• chr2-190894951-AT-ATT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_014905.5(GLS):​c.387-193delT variant causes a intron 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 0.44 (18644 hom., cov: 0)
• Consequence: GLS NM_014905.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 0 publications found

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]

GLS Gene-Disease associations (from GenCC):

• glutaminase deficiency

  Inheritance: AR Classification: DEFINITIVE, MODERATE Submitted by: ClinGen, Ambry Genetics
• global developmental delay, progressive ataxia, and elevated glutamine

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• infantile cataract, skin abnormalities, glutamate excess, and impaired intellectual development

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• developmental and epileptic encephalopathy, 71

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLS	NM_014905.5	c.387-193delT		intron_variant	Intron 1 of 17	ENST00000320717.8	NP_055720.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLS	ENST00000320717.8	c.387-200delT		intron_variant	Intron 1 of 17	1	NM_014905.5	ENSP00000317379.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67409 AN: 151610 Hom.: 18639 Cov.: 0

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.444 AC: 67433 AN: 151728 Hom.: 18644 Cov.: 0 AF XY: 0.447 AC XY: 33125 AN XY: 74152

African (AFR) AF: 0.136 AC: 5623 AN: 41316

American (AMR) AF: 0.408 AC: 6227 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1822 AN: 3462

East Asian (EAS) AF: 0.155 AC: 800 AN: 5162

South Asian (SAS) AF: 0.496 AC: 2390 AN: 4814

European-Finnish (FIN) AF: 0.669 AC: 7043 AN: 10530

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41885 AN: 67888

Other (OTH) AF: 0.453 AC: 953 AN: 2106

Alfa AF: 0.431 Hom.: 1602

Bravo AF: 0.410

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.053
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3217036; hg19: chr2-191759677;