dbSNP rs766499924: GK:c.*1A>G (chrX-30728743-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001205019.2(GK):c.*1A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000025 in 1,159,014 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000027 ( 0 hom. 12 hem. )

Consequence

GK
NM_001205019.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.820

Publications

0 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 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

GK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS2

High Hemizygotes in GnomAdExome4 at 12 AR,XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2 link	c.*1A>G		3_prime_UTR_variant	Exon 21 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.*1A>G		3_prime_UTR_variant	Exon 21 of 21	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111663

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

183052

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000267

AC:

AN:

1047351

Hom.:

Cov.:

AF XY:

0.0000369

AC XY:

AN XY:

325427

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25449

American (AMR)

AF:

0.00

AC:

AN:

35153

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19074

East Asian (EAS)

AF:

0.00

AC:

AN:

29991

South Asian (SAS)

AF:

0.00

AC:

AN:

53055

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40433

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3141

European-Non Finnish (NFE)

AF:

0.0000339

AC:

AN:

796734

Other (OTH)

AF:

0.0000226

AC:

AN:

44321

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111663

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33823

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30741

American (AMR)

AF:

0.00

AC:

AN:

10460

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3594

South Asian (SAS)

AF:

0.00

AC:

AN:

2671

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5991

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53132

Other (OTH)

AF:

0.00

AC:

AN:

1505

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Seizure;C0557874:Global developmental delay;C1854882:Absent speech

Uncertain:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.7

(source)

DANN

Benign

0.69

PhyloP100

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over