rs368255259
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BS1_SupportingBS2
The NM_015295.3(SMCHD1):c.4598T>C(p.Leu1533Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000301 in 1,429,584 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1533F) has been classified as Uncertain significance.
Frequency
Consequence
NM_015295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.4598T>C | p.Leu1533Ser | missense_variant | 37/48 | ENST00000320876.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.4598T>C | p.Leu1533Ser | missense_variant | 37/48 | 5 | NM_015295.3 | P2 | |
ENST00000583546.1 | n.370+44787A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000232 AC: 5AN: 215512Hom.: 0 AF XY: 0.00000848 AC XY: 1AN XY: 117954
GnomAD4 exome AF: 0.0000301 AC: 43AN: 1429584Hom.: 0 Cov.: 29 AF XY: 0.0000183 AC XY: 13AN XY: 711072
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Facioscapulohumeral muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 18, 2021 | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMCHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 289129). This variant is present in population databases (rs368255259, ExAC 0.009%). This sequence change replaces leucine with serine at codon 1533 of the SMCHD1 protein (p.Leu1533Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 30, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at