rs587784429
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 7P and 4B. PM1PM5PP2PP5_ModerateBS2
The NM_005445.4(SMC3):c.707G>A(p.Arg236His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R236P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_005445.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC3 | NM_005445.4 | c.707G>A | p.Arg236His | missense_variant | 9/29 | ENST00000361804.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC3 | ENST00000361804.5 | c.707G>A | p.Arg236His | missense_variant | 9/29 | 1 | NM_005445.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461278Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726974
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74306
ClinVar
Submissions by phenotype
Cornelia de Lange syndrome 3 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jul 13, 2023 | Criteria applied: PM1,PM5,PM2_SUP,PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at