X-30653779-G-C

Variant names:

• chrX-30653779-G-C
• rs12854653
• NM_001205019.2:c.78+164G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001205019.2(GK):​c.78+164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (20306 hom., 23786 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.173
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-30653779-G-C is Benign according to our data. Variant chrX-30653779-G-C is described in ClinVar as [Benign]. Clinvar id is 1281954.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.78+164G>C		intron_variant	Intron 1 of 20	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.78+164G>C		intron_variant	Intron 1 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.711 AC: 79239 AN: 111377 Hom.: 20301 Cov.: 24

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.530

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.712 AC: 79307 AN: 111431 Hom.: 20306 Cov.: 24 AF XY: 0.707 AC XY: 23786 AN XY: 33651

African (AFR) AF: 0.895 AC: 27526 AN: 30759

American (AMR) AF: 0.704 AC: 7517 AN: 10677

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 1684 AN: 2644

East Asian (EAS) AF: 0.647 AC: 2247 AN: 3473

South Asian (SAS) AF: 0.572 AC: 1545 AN: 2699

European-Finnish (FIN) AF: 0.677 AC: 4011 AN: 5925

Middle Eastern (MID) AF: 0.535 AC: 115 AN: 215

European-Non Finnish (NFE) AF: 0.630 AC: 33305 AN: 52856

Other (OTH) AF: 0.658 AC: 997 AN: 1515

Alfa AF: 0.691 Hom.: 5577

Bravo AF: 0.721

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 12, 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	-0.82
CADD	Benign	7.3
DANN	Benign	0.29
PhyloP100		-0.17
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12854653; hg19: chrX-30671896;