rs1555710171
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM4PP3PP5_Moderate
The NM_001083962.2(TCF4):c.1811_1822del(p.Pro604_Lys607del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TCF4
NM_001083962.2 inframe_deletion
NM_001083962.2 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
TCF4 (HGNC:11634): (transcription factor 4) This gene encodes transcription factor 4, a basic helix-loop-helix transcription factor. The encoded protein recognizes an Ephrussi-box ('E-box') binding site ('CANNTG') - a motif first identified in immunoglobulin enhancers. This gene is broadly expressed, and may play an important role in nervous system development. Defects in this gene are a cause of Pitt-Hopkins syndrome. In addition, an intronic CTG repeat normally numbering 10-37 repeat units can expand to >50 repeat units and cause Fuchs endothelial corneal dystrophy. Multiple alternatively spliced transcript variants that encode different proteins have been described. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_001083962.2
PM4
?
Nonframeshift variant in NON repetitive region in NM_001083962.2.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 18-55228903-AGCTTGGTCTGGG-A is Pathogenic according to our data. Variant chr18-55228903-AGCTTGGTCTGGG-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 520759.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCF4 | NM_001083962.2 | c.1811_1822del | p.Pro604_Lys607del | inframe_deletion | 18/20 | ENST00000354452.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCF4 | ENST00000354452.8 | c.1811_1822del | p.Pro604_Lys607del | inframe_deletion | 18/20 | 5 | NM_001083962.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 17, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at