chrX-30695846-A-G

Variant names:

• chrX-30695846-A-G
• rs619
• NM_001205019.2:c.553-196A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001205019.2(GK):​c.553-196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 111,664 control chromosomes in the GnomAD database, including 3,440 homozygotes. There are 9,683 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (3440 hom., 9683 hem., cov: 24)
• Consequence: GK NM_001205019.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.720
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-30695846-A-G is Benign according to our data. Variant chrX-30695846-A-G is described in ClinVar as Benign. ClinVar VariationId is 1250732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GK	NM_001205019.2	c.553-196A>G		intron_variant	Intron 6 of 20	ENST00000427190.6	NP_001191948.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GK	ENST00000427190.6	c.553-196A>G		intron_variant	Intron 6 of 20	5	NM_001205019.2	ENSP00000401720.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 32146 AN: 111613 Hom.: 3439 Cov.: 24

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.288 AC: 32152 AN: 111664 Hom.: 3440 Cov.: 24 AF XY: 0.286 AC XY: 9683 AN XY: 33870

African (AFR) AF: 0.197 AC: 6085 AN: 30856

American (AMR) AF: 0.287 AC: 3028 AN: 10560

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 721 AN: 2645

East Asian (EAS) AF: 0.409 AC: 1438 AN: 3519

South Asian (SAS) AF: 0.429 AC: 1162 AN: 2708

European-Finnish (FIN) AF: 0.407 AC: 2411 AN: 5931

Middle Eastern (MID) AF: 0.236 AC: 51 AN: 216

European-Non Finnish (NFE) AF: 0.316 AC: 16758 AN: 53018

Other (OTH) AF: 0.259 AC: 395 AN: 1525

Alfa AF: 0.320 Hom.: 7518

Bravo AF: 0.275

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
CADD	Benign	4.4
DANN	Benign	0.78
PhyloP100		0.72
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: rs619; hg19: chrX-30713963;