16-67610830-GAAAT-TC

Variant names:

• chr16-67610830-GAAAT-TC
• NM_006565.4:c.-3_2delGAAATinsTC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Supporting PM2 PP5_Moderate

The NM_006565.4(CTCF):​c.-3_2delGAAATinsTC​(p.Met1delinsSer) variant causes a start lost, conservative inframe deletion, synonymous 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, conservative_inframe_deletion, synonymous
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 7.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 177 CDS bases. Genomic position: 67611009. Lost 0.081 part of the original CDS.
• 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 rank	MANE	Protein	UniProt
CTCF	NM_006565.4	c.-3_2delGAAATinsTC	p.Met1delinsSer	start_lost, conservative_inframe_deletion, synonymous_variant	Exon 3 of 12	ENST00000264010.10	NP_006556.1
CTCF	NM_006565.4	c.-3_2delGAAATinsTC		5_prime_UTR_variant	Exon 3 of 12	ENST00000264010.10	NP_006556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTCF	ENST00000264010.10	c.-3_2delGAAATinsTC	p.Met1delinsSer	start_lost, conservative_inframe_deletion, synonymous_variant	Exon 3 of 12	1	NM_006565.4	ENSP00000264010.4
CTCF	ENST00000264010	c.-3_2delGAAATinsTC		5_prime_UTR_variant	Exon 3 of 12	1	NM_006565.4	ENSP00000264010.4

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

Submissions by phenotype

Intellectual disability-feeding difficulties-developmental delay-microcephaly syndrome Pathogenic:1

Jan 19, 2018

Centogene AG - the Rare Disease Company

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

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;