rs1554599065
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017780.4(CHD7):c.3490C>T(p.Gln1164Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q1164Q) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_017780.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD7 | NM_017780.4 | c.3490C>T | p.Gln1164Ter | stop_gained | 14/38 | ENST00000423902.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD7 | ENST00000423902.7 | c.3490C>T | p.Gln1164Ter | stop_gained | 14/38 | 5 | NM_017780.4 | P1 | |
CHD7 | ENST00000524602.5 | c.1717-33455C>T | intron_variant | 1 | |||||
CHD7 | ENST00000695853.1 | c.3490C>T | p.Gln1164Ter | stop_gained, NMD_transcript_variant | 14/37 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
CHARGE association Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 10, 2017 | This sequence change creates a premature translational stop signal at codon 1164 (p.Gln1164*) of the CHD7 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in CHD7 are known to be pathogenic (PMID: 16400610, 22461308). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at