10-100256287-C-A

Variant names:

• chr10-100256287-C-A
• rs2270962
• NM_018294.6:c.479G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018294.6(CWF19L1):​c.479G>T​(p.Cys160Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C160Y) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CWF19L1 NM_018294.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16272363).

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.479G>T	p.Cys160Phe	missense	Exon 5 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.479G>T	p.Cys160Phe	missense	Exon 5 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.68G>T	p.Cys23Phe	missense	Exon 5 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.479G>T	p.Cys160Phe	missense	Exon 5 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.479G>T	p.Cys160Phe	missense	Exon 5 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.479G>T	p.Cys160Phe	missense	Exon 5 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461690 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727154

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.00050	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.47	N
REVEL	Benign	0.051
Sift	Benign	0.037	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0	B
Vest4		0.099
MutPred		0.24		Loss of ubiquitination at K159 (P = 0.0755)
MVP		0.30
MPC		0.27
ClinPred		0.75	D
GERP RS		4.8
Varity_R		0.083
gMVP		0.68
Mutation Taster		=98/2	polymorphism

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: rs2270962; hg19: chr10-102016044;