dbSNP rs132630331: GK:p.Asn294Asp (chrX-30707584-A-G) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001205019.2(GK):c.880A>G(p.Asn294Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000102 in 977,318 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000010 ( 0 hom. 1 hem. )

Consequence

GK
NM_001205019.2 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.80

Publications

9 publications found

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:

GK-AS1 (HGNC:40255): (GK antisense RNA 1)

GK-AS1 links:

ENSG00000241886 (HGNC:):

ENSG00000241886 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

PP5

Variant X-30707584-A-G is Pathogenic according to our data. Variant chrX-30707584-A-G is described in ClinVar as Pathogenic. ClinVar VariationId is 10948.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2 link	c.880A>G	p.Asn294Asp	missense_variant	Exon 12 of 21	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6 link	c.880A>G	p.Asn294Asp	missense_variant	Exon 12 of 21	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000102

AC:

AN:

977318

Hom.:

Cov.:

AF XY:

0.00000351

AC XY:

AN XY:

284518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24139

American (AMR)

AF:

0.00

AC:

AN:

34708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18583

East Asian (EAS)

AF:

0.00

AC:

AN:

29512

South Asian (SAS)

AF:

0.00

AC:

AN:

50463

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40347

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3799

European-Non Finnish (NFE)

AF:

0.00000136

AC:

AN:

733728

Other (OTH)

AF:

0.00

AC:

AN:

42039

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Inborn glycerol kinase deficiency

Pathogenic:1

May 01, 2000

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

.;.;D;.

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Pathogenic

0.60

MetaRNN

Pathogenic

0.93

D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.5

H;.;H;.

PhyloP100

6.8

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.8

D;D;.;D

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

1.0

.;D;D;D

Vest4

0.74

MutPred

0.77

Gain of sheet (P = 0.0221);.;Gain of sheet (P = 0.0221);.;

MVP

0.97

MPC

2.4

ClinPred

1.0

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.90

gMVP

0.99

Mutation Taster

=11/89

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over