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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N294I) has been classified as Uncertain significance.

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001205019.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GK	NM_001205019.2	MANE Select	c.880A>G	p.Asn294Asp	missense	Exon 12 of 21	NP_001191948.1	P32189-3
GK	NM_001437590.1		c.946A>G	p.Asn316Asp	missense	Exon 12 of 21	NP_001424519.1	A0A8I5KXY7
GK	NM_001128127.3		c.862A>G	p.Asn288Asp	missense	Exon 11 of 20	NP_001121599.1	P32189-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GK	ENST00000427190.6	TSL:5 MANE Select	c.880A>G	p.Asn294Asp	missense	Exon 12 of 21	ENSP00000401720.2	P32189-3
GK	ENST00000378943.7	TSL:1	c.862A>G	p.Asn288Asp	missense	Exon 11 of 20	ENSP00000368226.3	P32189-2
GK	ENST00000378946.7	TSL:1	c.880A>G	p.Asn294Asp	missense	Exon 12 of 20	ENSP00000368229.3	P32189-4

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

ClinVar submissions

Significance:Pathogenic

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn glycerol kinase deficiency (1)

Computational scores

Source: dbNSFP v4.9

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

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.60

MetaRNN

Pathogenic

0.93

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.5

PhyloP100

6.8

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-4.8

REVEL

Pathogenic

0.83

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.74

MutPred

0.77

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over