X-30668045-T-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001205019.2(GK):​c.186T>C​(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 (★★).

Frequency

Genomes: 𝑓 0.0036 ( 0 hom., 115 hem., cov: 23)
Exomes 𝑓: 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

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
BS2
High Hemizygotes in GnomAd4 at 115 AR,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
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
GnomAD2 exomes
AF:
0.00120
AC:
220
AN:
183069
AF XY:
0.000886
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 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
African (AFR)
AF:
0.0142
AC:
355
AN:
24937
American (AMR)
AF:
0.000598
AC:
21
AN:
35119
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
18881
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29886
South Asian (SAS)
AF:
0.00
AC:
0
AN:
52540
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
40497
Middle Eastern (MID)
AF:
0.000286
AC:
1
AN:
3494
European-Non Finnish (NFE)
AF:
0.00000390
AC:
3
AN:
769877
Other (OTH)
AF:
0.000645
AC:
28
AN:
43408
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.461
Heterozygous variant carriers
0
16
32
47
63
79
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
20
40
60
80
100
<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:
0.00358
AC:
404
AN:
112824
Hom.:
0
Cov.:
23
AF XY:
0.00329
AC XY:
115
AN XY:
34964
show subpopulations
African (AFR)
AF:
0.0126
AC:
393
AN:
31145
American (AMR)
AF:
0.000564
AC:
6
AN:
10633
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2654
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3639
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2751
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6203
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
217
European-Non Finnish (NFE)
AF:
0.0000375
AC:
2
AN:
53361
Other (OTH)
AF:
0.00195
AC:
3
AN:
1537
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
15
31
46
62
77
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

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
PhyloP100
1.3
Mutation Taster
=298/2
polymorphism (auto)

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

Other links and lift over

dbSNP: rs45537438; hg19: chrX-30686162; API