4-860924-T-G

Variant names:

• chr4-860924-T-G
• rs4690339
• NM_005255.4:c.3167-1202A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005255.4(GAK):​c.3167-1202A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GAK NM_005255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.16
• Publications: 11 publications found

Genes affected

GAK (HGNC:4113): (cyclin G associated kinase) In all eukaryotes, the cell cycle is governed by cyclin-dependent protein kinases (CDKs), whose activities are regulated by cyclins and CDK inhibitors in a diverse array of mechanisms that involve the control of phosphorylation and dephosphorylation of Ser, Thr or Tyr residues. Cyclins are molecules that possess a consensus domain called the 'cyclin box.' In mammalian cells, 9 cyclin species have been identified, and they are referred to as cyclins A through I. Cyclin G is a direct transcriptional target of the p53 tumor suppressor gene product and thus functions downstream of p53. GAK is an association partner of cyclin G and CDK5. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAK	NM_005255.4	MANE Select	c.3167-1202A>C		intron	N/A	NP_005246.2
	GAK	NM_001318134.2		c.2930-1202A>C		intron	N/A	NP_001305063.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAK	ENST00000314167.9	TSL:1 MANE Select	c.3167-1202A>C		intron	N/A	ENSP00000314499.4
	GAK	ENST00000511163.5	TSL:1	c.2930-1202A>C		intron	N/A	ENSP00000421361.1
	GAK	ENST00000510799.1	TSL:1	c.524-1202A>C		intron	N/A	ENSP00000426062.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 9105

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.26
DANN	Benign	0.34
PhyloP100		-3.2

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: rs4690339; hg19: chr4-854712;