chr16-67610830-GAAAT-TC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_006565.4(CTCF):​c.-3_2delinsTC variant causes a start lost, 5 prime UTR change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CTCF
NM_006565.4 start_lost, 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.94
Variant links:
Genes affected
CTCF (HGNC:13723): (CCCTC-binding factor) This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression. Mutations in this gene have been associated with invasive breast cancers, prostate cancers, and Wilms' tumors. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 16-67610830-GAAAT-TC is Pathogenic according to our data. Variant chr16-67610830-GAAAT-TC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1333949.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CTCFNM_006565.4 linkuse as main transcriptc.-3_2delinsTC start_lost, 5_prime_UTR_variant 3/12 ENST00000264010.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CTCFENST00000264010.10 linkuse as main transcriptc.-3_2delinsTC start_lost, 5_prime_UTR_variant 3/121 NM_006565.4 P4P49711-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCentogene AG - the Rare Disease CompanyJan 19, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: chr16-67644733; API