10-100235758-G-T

Variant names:

• chr10-100235758-G-T
• rs2134272638
• NM_018294.6:c.1381C>A

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.1381C>A​(p.Gln461Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CWF19L1 NM_018294.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.18
• 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=0.19181594).

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.1381C>A	p.Gln461Lys	missense	Exon 13 of 14	NP_060764.3
	CWF19L1	NM_001303404.2		c.1261C>A	p.Gln421Lys	missense	Exon 12 of 13	NP_001290333.1
	CWF19L1	NM_001303405.2		c.970C>A	p.Gln324Lys	missense	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.1381C>A	p.Gln461Lys	missense	Exon 13 of 14	ENSP00000326411.6	Q69YN2-1
	CWF19L1	ENST00000950162.1		c.1381C>A	p.Gln461Lys	missense	Exon 13 of 14	ENSP00000620221.1
	CWF19L1	ENST00000950161.1		c.1378C>A	p.Gln460Lys	missense	Exon 13 of 14	ENSP00000620220.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455940 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724698

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109318

Other (OTH) AF: 0.0000166 AC: 1 AN: 60238

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.90
DEOGEN2	Benign	0.0024	T
Eigen	Benign	0.065
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		9.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.63	T
Sift4G	Benign	0.97	T
Polyphen		0.23	B
Vest4		0.26
MutPred		0.51		Gain of methylation at Q461 (P = 0.0059)
MVP		0.27
MPC		0.23
ClinPred		0.77	D
GERP RS		5.3
Varity_R		0.53
gMVP		0.54
Mutation Taster		=77/23	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: rs2134272638; hg19: chr10-101995515;