Variant 10-100236941-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018294.6(CWF19L1):c.1283C>T(p.Thr428Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,455,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CWF19L1
NM_018294.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Variant links:

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]

CWF19L1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.098700315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CWF19L1	NM_018294.6 linkuse as main transcript	c.1283C>T	p.Thr428Ile	missense_variant	12/14	ENST00000354105.10	NP_060764.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CWF19L1	ENST00000354105.10 linkuse as main transcript	c.1283C>T	p.Thr428Ile	missense_variant	12/14	1	NM_018294.6	ENSP00000326411	P1	Q69YN2-1
CWF19L1	ENST00000478047.1 linkuse as main transcript	n.1438C>T		non_coding_transcript_exon_variant	3/5	2
CWF19L1	ENST00000468709.5 linkuse as main transcript	c.*833C>T		3_prime_UTR_variant, NMD_transcript_variant	11/13	2		ENSP00000492991
CWF19L1	ENST00000482452.5 linkuse as main transcript	c.*670C>T		3_prime_UTR_variant, NMD_transcript_variant	10/13	5		ENSP00000492899

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000411

AC:

AN:

243544

Hom.:

AF XY:

0.00000760

AC XY:

AN XY:

131618

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1455284

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

723778

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.1283C>T (p.T428I) alteration is located in exon 12 (coding exon 12) of the CWF19L1 gene. This alteration results from a C to T substitution at nucleotide position 1283, causing the threonine (T) at amino acid position 428 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0025

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

M_CAP

Benign

0.0094

MetaRNN

Benign

0.099

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.4

REVEL

Benign

0.027

Sift

Benign

0.17

Sift4G

Benign

0.19

Polyphen

0.016

Vest4

0.19

MutPred

0.28

Loss of catalytic residue at T428 (P = 0.0023);

MVP

0.25

MPC

0.20

ClinPred

0.096

GERP RS

3.3

Varity_R

0.034

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over