NM_001205019.2:c.78+9G>A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001205019.2(GK):​c.78+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,194,119 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 5 hem., cov: 24)
Exomes 𝑓: 0.00015 ( 0 hom. 52 hem. )

Consequence

GK
NM_001205019.2 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.474
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant X-30653624-G-A is Benign according to our data. Variant chrX-30653624-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730465.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 5 XL geneVariant has number of hemizygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GKNM_001205019.2 linkc.78+9G>A intron_variant Intron 1 of 20 ENST00000427190.6 NP_001191948.1 P32189-3B4DH54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GKENST00000427190.6 linkc.78+9G>A intron_variant Intron 1 of 20 5 NM_001205019.2 ENSP00000401720.2 P32189-3

Frequencies

GnomAD3 genomes
AF:
0.000107
AC:
12
AN:
112335
Hom.:
0
Cov.:
24
AF XY:
0.000145
AC XY:
5
AN XY:
34497
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:
0.000281
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000325
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000169
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000104
AC:
19
AN:
182782
Hom.:
0
AF XY:
0.0000888
AC XY:
6
AN XY:
67604
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000365
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000188
Gnomad NFE exome
AF:
0.000184
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000147
AC:
159
AN:
1081784
Hom.:
0
Cov.:
28
AF XY:
0.000149
AC XY:
52
AN XY:
348096
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000148
Gnomad4 NFE exome
AF:
0.000172
Gnomad4 OTH exome
AF:
0.000241
GnomAD4 genome
AF:
0.000107
AC:
12
AN:
112335
Hom.:
0
Cov.:
24
AF XY:
0.000145
AC XY:
5
AN XY:
34497
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000281
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000325
Gnomad4 NFE
AF:
0.000169
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000869

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

GK-related disorder Benign:1
Mar 02, 2019
PreventionGenetics, part of Exact Sciences
Significance: Likely benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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

not provided Benign:1
Feb 07, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely 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
-0.62
CADD
Benign
7.8
DANN
Benign
0.92
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373147022; hg19: chrX-30671741; COSMIC: COSV104701429; API