Variant X-30668045-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001205019.2(GK):c.186T>C(p.His62His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,131,463 control chromosomes in the GnomAD database, including 2 homozygotes. There are 208 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., 115 hem., cov: 23)

Exomes 𝑓: 0.00040 ( 2 hom. 93 hem. )

Consequence

GK
NM_001205019.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant X-30668045-T-C is Benign according to our data. Variant chrX-30668045-T-C is described in ClinVar as [Benign]. Clinvar id is 711787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.26 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00358 (404/112824) while in subpopulation AFR AF= 0.0126 (393/31145). AF 95% confidence interval is 0.0116. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 115 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2 link	c.186T>C	p.His62His	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.186T>C	p.His62His	synonymous_variant	Exon 3 of 21	5	NM_001205019.2	ENSP00000401720.2		P32189-3

Frequencies

GnomAD3 genomes

AF:

0.00359

AC:

405

AN:

112770

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

115

AN XY:

34900

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000565

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00198

GnomAD3 exomes

AF:

0.00120

AC:

220

AN:

183069

Hom.:

AF XY:

0.000886

AC XY:

AN XY:

67685

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.000511

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000368

Gnomad OTH exome

AF:

0.000222

GnomAD4 exome

AF:

0.000401

AC:

408

AN:

1018639

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

AN XY:

308655

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.000598

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000390

Gnomad4 OTH exome

AF:

0.000645

GnomAD4 genome

AF:

0.00358

AC:

404

AN:

112824

Hom.:

Cov.:

AF XY:

0.00329

AC XY:

115

AN XY:

34964

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.000564

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000375

Gnomad4 OTH

AF:

0.00195

Alfa

AF:

0.00213

Hom.:

Bravo

AF:

0.00425

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

GK-related disorder

Benign:1

Apr 14, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.4

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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