20-57498618-C-A

Variant names:

• chr20-57498618-C-A
• rs192956817
• NM_001386993.1:c.1924G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_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. 16/22 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07763779).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	NM_001386993.1	MANE Select	c.1924G>T	p.Ala642Ser	missense	Exon 11 of 11	NP_001373922.1	Q8NI51-1
	CTCFL	NM_001269043.2		c.1924G>T	p.Ala642Ser	missense	Exon 11 of 12	NP_001255972.1	Q8NI51-7
	CTCFL	NM_001269040.2		c.1924G>T	p.Ala642Ser	missense	Exon 11 of 11	NP_001255969.1	Q8NI51-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTCFL	ENST00000243914.8	TSL:1 MANE Select	c.1924G>T	p.Ala642Ser	missense	Exon 11 of 11	ENSP00000243914.3	Q8NI51-1
	CTCFL	ENST00000423479.7	TSL:1	c.1924G>T	p.Ala642Ser	missense	Exon 11 of 12	ENSP00000415579.2	Q8NI51-7
	CTCFL	ENST00000371196.6	TSL:1	c.1924G>T	p.Ala642Ser	missense	Exon 11 of 11	ENSP00000360239.2	Q8NI51-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.045
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.0040
Sift	Benign	0.21	T
Sift4G	Benign	0.90	T
Polyphen		0.028	B
Vest4		0.23
MutPred		0.23		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs192956817; hg19: chr20-56073674;