16-30902252-C-T

Variant names:

• chr16-30902252-C-T
• rs727502950
• NM_001330.5:c.319C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTF1 NM_001330.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0520

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28011882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTF1	NM_001330.5	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 3	ENST00000279804.3	NP_001321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTF1	ENST00000279804.3	c.319C>T	p.Arg107Cys	missense_variant	Exon 3 of 3	1	NM_001330.5	ENSP00000279804.2
CTF1	ENST00000395019.3	c.316C>T	p.Arg106Cys	missense_variant	Exon 3 of 3	1		ENSP00000378465.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 959156 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 452416

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The Arg107Cys variant in CTF1 has not been previously reported in any other fami lies with cardiomyopathy. Data from large population studies is insufficient to assess the frequency of this variant. Arginine (Arg) at position 107 is not cons erved in evolution, suggesting that a change may be tolerated. Additional compu tational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. At this time, additional information is needed to fully assess the clinical signifi cance of the Arg107Cys variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.68	T;T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.28
Sift	Benign	0.14	T;T
Sift4G	Uncertain	0.035	D;D
Polyphen		0.99	D;.
Vest4		0.050
MutPred		0.37		Loss of MoRF binding (P = 0.014);.;
MVP		0.89
MPC		0.65
ClinPred		0.46	T
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

LitVar

Other links and lift over

dbSNP: rs727502950; hg19: chr16-30913573;