X-30670598-ATT-A

Variant names:

• chrX-30670598-ATT-A
• rs34172820
• NM_001205019.2:c.259+2490_259+2491delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001205019.2(GK):​c.259+2490_259+2491delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (1646 hom., 5796 hem., cov: 16)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149
• Publications: 0 publications found

Genes affected

GK (HGNC:4289): (glycerol kinase) The protein encoded by this gene belongs to the FGGY kinase family. This protein is a key enzyme in the regulation of glycerol uptake and metabolism. It catalyzes the phosphorylation of glycerol by ATP, yielding ADP and glycerol-3-phosphate. Mutations in this gene are associated with glycerol kinase deficiency (GKD). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

GK Gene-Disease associations (from GenCC):

• inborn glycerol kinase deficiency

  Inheritance: AR, XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant X-30670598-ATT-A is Benign according to our data. Variant chrX-30670598-ATT-A is described in ClinVar as [Benign]. Clinvar id is 1235625.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.259+2490_259+2491delTT		intron_variant	Intron 3 of 20	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.259+2481_259+2482delTT		intron_variant	Intron 3 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.195 AC: 20735 AN: 106175 Hom.: 1650 Cov.: 16

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.195 AC: 20738 AN: 106195 Hom.: 1646 Cov.: 16 AF XY: 0.194 AC XY: 5796 AN XY: 29933

African (AFR) AF: 0.0977 AC: 2865 AN: 29322

American (AMR) AF: 0.273 AC: 2695 AN: 9889

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 667 AN: 2569

East Asian (EAS) AF: 0.227 AC: 767 AN: 3377

South Asian (SAS) AF: 0.115 AC: 286 AN: 2482

European-Finnish (FIN) AF: 0.208 AC: 1037 AN: 4974

Middle Eastern (MID) AF: 0.201 AC: 40 AN: 199

European-Non Finnish (NFE) AF: 0.232 AC: 11903 AN: 51326

Other (OTH) AF: 0.195 AC: 273 AN: 1403

Alfa AF: 0.0762 Hom.: 297

Bravo AF: 0.200

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 20, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.15
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: rs34172820; hg19: chrX-30688715;