NM_001205019.2:c.186T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001205019.2(GK):ā€‹c.186T>Cā€‹(p.His62His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000718 in 1,131,463 control chromosomes in the GnomAD database, including 2 homozygotes. There are 208 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0036 ( 0 hom., 115 hem., cov: 23)
Exomes š‘“: 0.00040 ( 2 hom. 93 hem. )

Consequence

GK
NM_001205019.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.26
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
Variant X-30668045-T-C is Benign according to our data. Variant chrX-30668045-T-C is described in ClinVar as [Benign]. Clinvar id is 711787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.26 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00358 (404/112824) while in subpopulation AFR AF= 0.0126 (393/31145). AF 95% confidence interval is 0.0116. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 115 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GKNM_001205019.2 linkc.186T>C p.His62His synonymous_variant Exon 3 of 21 ENST00000427190.6 NP_001191948.1 P32189-3B4DH54

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GKENST00000427190.6 linkc.186T>C p.His62His synonymous_variant Exon 3 of 21 5 NM_001205019.2 ENSP00000401720.2 P32189-3

Frequencies

GnomAD3 genomes
AF:
0.00359
AC:
405
AN:
112770
Hom.:
0
Cov.:
23
AF XY:
0.00330
AC XY:
115
AN XY:
34900
show subpopulations
Gnomad AFR
AF:
0.0127
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000565
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:
0.0000375
Gnomad OTH
AF:
0.00198
GnomAD3 exomes
AF:
0.00120
AC:
220
AN:
183069
Hom.:
0
AF XY:
0.000886
AC XY:
60
AN XY:
67685
show subpopulations
Gnomad AFR exome
AF:
0.0154
Gnomad AMR exome
AF:
0.000511
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000368
Gnomad OTH exome
AF:
0.000222
GnomAD4 exome
AF:
0.000401
AC:
408
AN:
1018639
Hom.:
2
Cov.:
22
AF XY:
0.000301
AC XY:
93
AN XY:
308655
show subpopulations
Gnomad4 AFR exome
AF:
0.0142
Gnomad4 AMR exome
AF:
0.000598
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000390
Gnomad4 OTH exome
AF:
0.000645
GnomAD4 genome
AF:
0.00358
AC:
404
AN:
112824
Hom.:
0
Cov.:
23
AF XY:
0.00329
AC XY:
115
AN XY:
34964
show subpopulations
Gnomad4 AFR
AF:
0.0126
Gnomad4 AMR
AF:
0.000564
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000375
Gnomad4 OTH
AF:
0.00195
Alfa
AF:
0.00213
Hom.:
9
Bravo
AF:
0.00425

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

GK-related disorder Benign:1
Apr 14, 2020
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
CADD
Benign
2.4
DANN
Benign
0.70

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

LitVar

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

Other links and lift over

dbSNP: rs45537438; hg19: chrX-30686162; API