Genetic Variant CTCFL:p.Glu619Asp (chr20-57498685-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001386993.1(CTCFL):c.1857G>C(p.Glu619Asp) 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. 16/22 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. E619V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CTCFL
NM_001386993.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.118

Publications

1 publications found

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]

CTCFL links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06280607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386993.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCFL	NM_001386993.1	MANE Select	c.1857G>C	p.Glu619Asp	missense	Exon 11 of 11	NP_001373922.1	Q8NI51-1
CTCFL	NM_001269043.2		c.1857G>C	p.Glu619Asp	missense	Exon 11 of 12	NP_001255972.1	Q8NI51-7
CTCFL	NM_001269040.2		c.1857G>C	p.Glu619Asp	missense	Exon 11 of 11	NP_001255969.1	Q8NI51-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.1857G>C	p.Glu619Asp	missense	Exon 11 of 11	ENSP00000243914.3	Q8NI51-1
CTCFL	ENST00000423479.7	TSL:1	c.1857G>C	p.Glu619Asp	missense	Exon 11 of 12	ENSP00000415579.2	Q8NI51-7
CTCFL	ENST00000371196.6	TSL:1	c.1857G>C	p.Glu619Asp	missense	Exon 11 of 11	ENSP00000360239.2	Q8NI51-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249744

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

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

0.093

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.56

DEOGEN2

Benign

0.025

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.53

M_CAP

Benign

0.0020

MetaRNN

Benign

0.063

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.11

PhyloP100

0.12

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.22

REVEL

Benign

0.0080

Sift

Benign

0.15

Sift4G

Benign

0.41

Polyphen

0.0060

Vest4

0.16

MutPred

0.21

Gain of glycosylation at T622 (P = 0.1441)

MVP

0.13

MPC

0.50

ClinPred

0.034

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.058

Mutation Taster

=99/1

polymorphism

(source)

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