Variant X-30668024-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001205019.2(GK):c.165G>A(p.Gln55Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,089,656 control chromosomes in the GnomAD database, including 1,886 homozygotes. There are 19,090 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 173 hom., 1753 hem., cov: 23)

Exomes 𝑓: 0.065 ( 1713 hom. 17337 hem. )

Consequence

GK
NM_001205019.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.14

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant X-30668024-G-A is Benign according to our data. Variant chrX-30668024-G-A is described in ClinVar as [Benign]. Clinvar id is 590201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-30668024-G-A is described in Lovd as [Benign]. Variant chrX-30668024-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2 link	c.165G>A	p.Gln55Gln	synonymous_variant	Exon 3 of 21	ENST00000427190.6	NP_001191948.1	P32189-3B4DH54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6 link	c.165G>A	p.Gln55Gln	synonymous_variant	Exon 3 of 21	5	NM_001205019.2	ENSP00000401720.2		P32189-3

Frequencies

GnomAD3 genomes

AF:

0.0532

AC:

5982

AN:

112368

Hom.:

173

Cov.:

AF XY:

0.0507

AC XY:

1753

AN XY:

34552

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0748

Gnomad AMR

AF:

0.0640

Gnomad ASJ

AF:

0.0823

Gnomad EAS

AF:

0.000275

Gnomad SAS

AF:

0.0247

Gnomad FIN

AF:

0.0589

Gnomad MID

AF:

0.0628

Gnomad NFE

AF:

0.0776

Gnomad OTH

AF:

0.0706

GnomAD3 exomes

AF:

0.0518

AC:

9457

AN:

182677

Hom.:

208

AF XY:

0.0523

AC XY:

3521

AN XY:

67331

show subpopulations

Gnomad AFR exome

AF:

0.00890

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0804

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.0232

Gnomad FIN exome

AF:

0.0639

Gnomad NFE exome

AF:

0.0744

Gnomad OTH exome

AF:

0.0626

GnomAD4 exome

AF:

0.0647

AC:

63217

AN:

977235

Hom.:

1713

Cov.:

AF XY:

0.0593

AC XY:

17337

AN XY:

292207

show subpopulations

Gnomad4 AFR exome

AF:

0.00829

Gnomad4 AMR exome

AF:

0.0370

Gnomad4 ASJ exome

AF:

0.0766

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0640

Gnomad4 NFE exome

AF:

0.0735

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0532

AC:

5980

AN:

112421

Hom.:

173

Cov.:

AF XY:

0.0506

AC XY:

1753

AN XY:

34615

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.0640

Gnomad4 ASJ

AF:

0.0823

Gnomad4 EAS

AF:

0.000275

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.0589

Gnomad4 NFE

AF:

0.0775

Gnomad4 OTH

AF:

0.0698

Alfa

AF:

0.0685

Hom.:

741

Bravo

AF:

0.0518

EpiCase

AF:

0.0831

EpiControl

AF:

0.0798

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases

Benign:1

Sep 07, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

3.7

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over