X-153672170-CTC-TTT

Variant names:

• chrX-153672170-CTC-TTT
• NM_001366977.1:c.229_231delGAGinsAAA
• PNCK p.Glu77Lys

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001366977.1(PNCK):​c.229_231delGAGinsAAA​(p.Glu77Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88
• Publications: 0 publications found

Genes affected

PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366977.1. 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
	PNCK	NM_001366977.1	MANE Select	c.229_231delGAGinsAAA	p.Glu77Lys	missense	N/A	NP_001353906.1	Q6P2M8-1
	PNCK	NM_001039582.3		c.478_480delGAGinsAAA	p.Glu160Lys	missense	N/A	NP_001034671.3	Q6P2M8-5
	PNCK	NM_001135740.2		c.280_282delGAGinsAAA	p.Glu94Lys	missense	N/A	NP_001129212.1	Q6P2M8-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNCK	ENST00000340888.8	TSL:5 MANE Select	c.229_231delGAGinsAAA	p.Glu77Lys	missense	N/A	ENSP00000340586.4	Q6P2M8-1
	PNCK	ENST00000472324.5	TSL:1	n.341_343delGAGinsAAA		non_coding_transcript_exon	Exon 4 of 8
	PNCK	ENST00000418241.5	TSL:3	c.249_251delGAGinsAAA	p.TrpArg83*	stop_gained	N/A	ENSP00000411267.1	C9J8P0

Frequencies

GnomAD3 genomes Cov.: 24

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

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-152937625;