20-20052352-AGT-TGC

Variant names:

• chr20-20052352-AGT-TGC
• ENST00000377340.6:c.472_474delACTinsGCA
• CRNKL1 p.Thr158Ala

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_016652.6(CRNKL1):​c.472_474delACTinsGCA​(p.Thr158Ala) variant causes a missense change involving the alteration of a non-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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CRNKL1 NM_016652.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.773
• Publications: 0 publications found

Genes affected

CRNKL1 (HGNC:15762): (crooked neck pre-mRNA splicing factor 1) The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

CFAP61 (HGNC:15872): (cilia and flagella associated protein 61) Predicted to be involved in cilium movement and cilium organization. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.87994 (below the threshold of 3.09). Trascript score misZ: 1.501 (below the threshold of 3.09).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016652.6. 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
	CRNKL1	NM_001278628.2	MANE Select	c.-12_-10delACTinsGCA		5_prime_UTR	Exon 1 of 14	NP_001265557.1	Q9BZJ0-2
	CRNKL1	NM_016652.6		c.472_474delACTinsGCA	p.Thr158Ala	missense	N/A	NP_057736.4
	CRNKL1	NM_001278625.2		c.436_438delACTinsGCA	p.Thr146Ala	missense	N/A	NP_001265554.1	Q5JY65

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRNKL1	ENST00000377340.6	TSL:1	c.472_474delACTinsGCA	p.Thr158Ala	missense	N/A	ENSP00000366557.2	Q9BZJ0-1
	CRNKL1	ENST00000377327.8	TSL:1	c.436_438delACTinsGCA	p.Thr146Ala	missense	N/A	ENSP00000366544.4	Q5JY65
	CRNKL1	ENST00000536226.2	TSL:1 MANE Select	c.-12_-10delACTinsGCA		5_prime_UTR	Exon 1 of 14	ENSP00000440733.1	Q9BZJ0-2

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.77

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: chr20-20032996;