rs886039917
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_001273.5(CHD4):c.3380G>A(p.Arg1127Gln) variant causes a missense change involving the alteration of a 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 (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CHD4
NM_001273.5 missense
NM_001273.5 missense
Scores
13
1
Clinical Significance
Conservation
PhyloP100: 7.79
Genes affected
CHD4 (HGNC:1919): (chromodomain helicase DNA binding protein 4) The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Somatic mutations in this gene are associated with serous endometrial tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a domain Helicase C-terminal (size 149) in uniprot entity CHD4_HUMAN there are 28 pathogenic changes around while only 1 benign (97%) in NM_001273.5
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CHD4
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.915
PP5
?
Variant 12-6588383-C-T is Pathogenic according to our data. Variant chr12-6588383-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 266126.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-6588383-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHD4 | NM_001273.5 | c.3380G>A | p.Arg1127Gln | missense_variant | 23/40 | ENST00000544040.7 | |
CHD4 | NM_001297553.2 | c.3359G>A | p.Arg1120Gln | missense_variant | 22/39 | ||
CHD4 | NM_001363606.2 | c.3341G>A | p.Arg1114Gln | missense_variant | 23/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHD4 | ENST00000544040.7 | c.3380G>A | p.Arg1127Gln | missense_variant | 23/40 | 5 | NM_001273.5 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Sifrim-Hitz-Weiss syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
REVEL
Pathogenic
Polyphen
1.0, 0.98, 0.98
.;.;D;D;.;.;.;.;D;.;.;.
Vest4
0.96
MutPred
0.73
.;.;.;Loss of methylation at R1127 (P = 0.0155);.;.;.;.;Loss of methylation at R1127 (P = 0.0155);.;Loss of methylation at R1127 (P = 0.0155);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at