rs1057519644
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_015295.3(SMCHD1):c.410G>A(p.Gly137Glu) variant causes a missense change. 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
SMCHD1
NM_015295.3 missense
NM_015295.3 missense
Scores
6
10
3
Clinical Significance
Conservation
PhyloP100: 6.37
Genes affected
SMCHD1 (HGNC:29090): (structural maintenance of chromosomes flexible hinge domain containing 1) This gene encodes a protein which contains a hinge region domain found in members of the SMC (structural maintenance of chromosomes) protein family. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the SMCHD1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 23 curated pathogenic missense variants (we use a threshold of 10). The gene has 10 curated benign missense variants. Gene score misZ: 3.6318 (above the threshold of 3.09). Trascript score misZ: 3.965 (above the threshold of 3.09). GenCC associations: The gene is linked to facioscapulohumeral muscular dystrophy, arhinia, choanal atresia, and microphthalmia, hyposmia-nasal and ocular hypoplasia-hypogonadotropic hypogonadism syndrome.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.795
PP5
Variant 18-2667017-G-A is Pathogenic according to our data. Variant chr18-2667017-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 375765.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr18-2667017-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.410G>A | p.Gly137Glu | missense_variant | Exon 3 of 48 | ENST00000320876.11 | NP_056110.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.410G>A | p.Gly137Glu | missense_variant | Exon 3 of 48 | 5 | NM_015295.3 | ENSP00000326603.7 | ||
SMCHD1 | ENST00000688342.1 | c.410G>A | p.Gly137Glu | missense_variant | Exon 3 of 47 | ENSP00000508422.1 | ||||
SMCHD1 | ENST00000684915.1 | n.567G>A | non_coding_transcript_exon_variant | Exon 3 of 14 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Arrhinia with choanal atresia and microphthalmia syndrome Pathogenic:2
Dec 01, 2012
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
-
MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: research
- -
Facioscapulohumeral muscular dystrophy 2 Pathogenic:1
Dec 01, 2012
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of solvent accessibility (P = 0.024);
MVP
MPC
ClinPred
D
GERP RS
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