chr20-57519356-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001386993.1(CTCFL):c.776G>A(p.Cys259Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CTCFL
NM_001386993.1 missense
NM_001386993.1 missense
Scores
7
8
3
Clinical Significance
Conservation
PhyloP100: 7.68
Genes affected
CTCFL (HGNC:16234): (CCCTC-binding factor like) CCCTC-binding factor (CTCF), an 11-zinc-finger factor involved in gene regulation, utilizes different zinc fingers to bind varying DNA target sites. CTCF forms methylation-sensitive insulators that regulate X-chromosome inactivation. This gene is a paralog of CTCF and appears to be expressed primarily in the cytoplasm of spermatocytes, unlike CTCF which is expressed primarily in the nucleus of somatic cells. CTCF and the protein encoded by this gene are normally expressed in a mutually exclusive pattern that correlates with resetting of methylation marks during male germ cell differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.953
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTCFL | NM_001386993.1 | c.776G>A | p.Cys259Tyr | missense_variant | 4/11 | ENST00000243914.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTCFL | ENST00000243914.8 | c.776G>A | p.Cys259Tyr | missense_variant | 4/11 | 1 | NM_001386993.1 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251400Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135874
GnomAD3 exomes
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727142
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
AC:
1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 07, 2023 | The c.776G>A (p.C259Y) alteration is located in exon 4 (coding exon 3) of the CTCFL gene. This alteration results from a G to A substitution at nucleotide position 776, causing the cysteine (C) at amino acid position 259 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;.;D;.;D;D;D;D;D;D;D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M;M;M;.;M;.;M;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.;D;D;D;.;.;D;D;D;.;.;.
REVEL
Uncertain
Sift
Benign
D;.;.;D;D;D;.;.;D;D;T;.;.;.
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;D;.;D;D;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);.;Gain of phosphorylation at C259 (P = 0.0546);.;Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);Gain of phosphorylation at C259 (P = 0.0546);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at