rs192956817

Variant summary

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

The NM_001386993.1(CTCFL):​c.1924G>T​(p.Ala642Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A642T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CTCFL
NM_001386993.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450
Variant links:
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 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=0.07763779).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTCFLNM_001386993.1 linkc.1924G>T p.Ala642Ser missense_variant Exon 11 of 11 ENST00000243914.8 NP_001373922.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTCFLENST00000243914.8 linkc.1924G>T p.Ala642Ser missense_variant Exon 11 of 11 1 NM_001386993.1 ENSP00000243914.3 Q8NI51-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
4.7
DANN
Benign
0.83
DEOGEN2
Benign
0.034
.;T;T;.;T;T
Eigen
Benign
-0.92
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.50
T;.;.;T;.;T
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.078
T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.81
L;L;L;.;L;L
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-0.12
N;.;.;N;N;N
REVEL
Benign
0.0040
Sift
Benign
0.21
T;.;.;T;T;T
Sift4G
Benign
0.90
T;T;T;T;T;T
Polyphen
0.028
.;B;B;.;B;B
Vest4
0.23
MutPred
0.23
Gain of phosphorylation at A642 (P = 0.0427);Gain of phosphorylation at A642 (P = 0.0427);Gain of phosphorylation at A642 (P = 0.0427);.;Gain of phosphorylation at A642 (P = 0.0427);Gain of phosphorylation at A642 (P = 0.0427);
MVP
0.26
MPC
0.50
ClinPred
0.048
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.064
gMVP
0.027

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-56073674; API