chr10-100235671-CA-C

Variant names:

• chr10-100235671-CA-C
• rs1389916079
• NM_018294.6:c.1467delT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_018294.6(CWF19L1):​c.1467delT​(p.Phe489LeufsTer64) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CWF19L1 NM_018294.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 0 publications found

Genes affected

CWF19L1 (HGNC:25613): (CWF19 like cell cycle control factor 1) This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

CHUK-DT (HGNC:55813): (CHUK divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0928 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018294.6. 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
	CWF19L1	NM_018294.6	MANE Select	c.1467delT	p.Phe489LeufsTer64	frameshift	Exon 13 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.1347delT	p.Phe449LeufsTer64	frameshift	Exon 12 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.1056delT	p.Phe352LeufsTer64	frameshift	Exon 13 of 14	NP_001290334.1	Q69YN2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CWF19L1	ENST00000354105.10	TSL:1 MANE Select	c.1467delT	p.Phe489LeufsTer64	frameshift	Exon 13 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1467delT	p.Phe489LeufsTer64	frameshift	Exon 13 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1464delT	p.Phe488LeufsTer64	frameshift	Exon 13 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2

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: rs1389916079; hg19: chr10-101995428;