1-6106629-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_015557.3(CHD5):c.5729C>T(p.Pro1910Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,427,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015557.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CHD5 | ENST00000262450.8 | c.5729C>T | p.Pro1910Leu | missense_variant | Exon 39 of 42 | 1 | NM_015557.3 | ENSP00000262450.3 | ||
CHD5 | ENST00000496404.1 | n.*769C>T | non_coding_transcript_exon_variant | Exon 31 of 34 | 2 | ENSP00000433676.1 | ||||
CHD5 | ENST00000496404.1 | n.*769C>T | 3_prime_UTR_variant | Exon 31 of 34 | 2 | ENSP00000433676.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 152160Hom.: 0 Cov.: 32 FAILED QC
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1427044Hom.: 0 Cov.: 34 AF XY: 0.00000283 AC XY: 2AN XY: 706822
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: CHD5 c.5729C>T (p.Pro1910Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 194144 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5729C>T in individuals affected with Parenti-Mignot Neurodevelopmental Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 3144161). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Inborn genetic diseases Uncertain:1
The c.5729C>T (p.P1910L) alteration is located in exon 39 (coding exon 39) of the CHD5 gene. This alteration results from a C to T substitution at nucleotide position 5729, causing the proline (P) at amino acid position 1910 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at