Genetic Variant CTF1:p.Arg107Cys (chr16-30902252-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330.5(CTF1):c.319C>T(p.Arg107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTF1
NM_001330.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0520

Publications

0 publications found

Variant links:

Genes affected

CTF1 (HGNC:2499): (cardiotrophin 1) The protein encoded by this gene is a secreted cytokine that induces cardiac myocyte hypertrophy in vitro. It has been shown to bind and activate the ILST/gp130 receoptor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

CTF1 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

CTF1 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28011882).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTF1	NM_001330.5	MANE Select	c.319C>T	p.Arg107Cys	missense	Exon 3 of 3	NP_001321.1	Q16619-1
CTF1	NM_001142544.3		c.316C>T	p.Arg106Cys	missense	Exon 3 of 3	NP_001136016.1	Q16619-2
CTF1	NR_165660.1		n.457C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTF1	ENST00000279804.3	TSL:1 MANE Select	c.319C>T	p.Arg107Cys	missense	Exon 3 of 3	ENSP00000279804.2	Q16619-1
	CTF1	ENST00000395019.3	TSL:1	c.316C>T	p.Arg106Cys	missense	Exon 3 of 3	ENSP00000378465.3	Q16619-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

959156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

452416

African (AFR)

AF:

0.00

AC:

AN:

18754

American (AMR)

AF:

0.00

AC:

AN:

5126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9130

East Asian (EAS)

AF:

0.00

AC:

AN:

13330

South Asian (SAS)

AF:

0.00

AC:

AN:

19312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2288

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

844018

Other (OTH)

AF:

0.00

AC:

AN:

34888

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.62

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.2

PhyloP100

-0.052

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.9

REVEL

Benign

0.28

Sift

Benign

0.14

Sift4G

Uncertain

0.035

Polyphen

0.99

Vest4

0.050

MutPred

0.37

Loss of MoRF binding (P = 0.014)

MVP

0.89

MPC

0.65

ClinPred

0.46

GERP RS

3.7

Varity_R

0.17

gMVP

0.41

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over