Genetic Variant GK:c.153-92A>C (chrX-30667920-A-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001205019.2(GK):c.153-92A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 553,588 control chromosomes in the GnomAD database, including 140 homozygotes. There are 1,155 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.026 ( 98 hom., 753 hem., cov: 24)

Exomes 𝑓: 0.0036 ( 42 hom. 402 hem. )

Consequence

GK
NM_001205019.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.339

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-30667920-A-C is Benign according to our data. Variant chrX-30667920-A-C is described in ClinVar as [Benign]. Clinvar id is 1286744.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2 link	c.153-92A>C		intron_variant	Intron 2 of 20	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.153-92A>C		intron_variant	Intron 2 of 20	5	NM_001205019.2	ENSP00000401720.2		P32189-3

Frequencies

GnomAD3 genomes

AF:

0.0260

AC:

2911

AN:

112047

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0896

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00942

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:

0.000620

Gnomad OTH

AF:

0.0153

GnomAD4 exome

AF:

0.00364

AC:

1607

AN:

441491

Hom.:

AF XY:

0.00263

AC XY:

402

AN XY:

152931

show subpopulations

African (AFR)

AF:

0.0882

AC:

1152

AN:

13061

American (AMR)

AF:

0.00567

AC:

162

AN:

28592

Ashkenazi Jewish (ASJ)

AF:

0.0000681

AC:

AN:

14677

East Asian (EAS)

AF:

0.00

AC:

AN:

25075

South Asian (SAS)

AF:

0.000389

AC:

AN:

38591

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37792

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

1763

European-Non Finnish (NFE)

AF:

0.000326

AC:

AN:

258055

Other (OTH)

AF:

0.00783

AC:

187

AN:

23885

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0260

AC:

2912

AN:

112097

Hom.:

Cov.:

AF XY:

0.0219

AC XY:

753

AN XY:

34317

show subpopulations

African (AFR)

AF:

0.0895

AC:

2758

AN:

30831

American (AMR)

AF:

0.00932

AC:

AN:

10520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3618

South Asian (SAS)

AF:

0.00

AC:

AN:

2766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6078

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000620

AC:

AN:

53202

Other (OTH)

AF:

0.0151

AC:

AN:

1525

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

109

217

326

434

543

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0559

Hom.:

396

Bravo

AF:

0.0304

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 21, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.0

(source)

DANN

Benign

0.41

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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X-30667920-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over