rs1057519644
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP2PP3PP5
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 Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 4 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_015295.3
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SMCHD1
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.410G>A | p.Gly137Glu | missense_variant | 3/48 | ENST00000320876.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.410G>A | p.Gly137Glu | missense_variant | 3/48 | 5 | NM_015295.3 | P2 | |
SMCHD1 | ENST00000688342.1 | c.410G>A | p.Gly137Glu | missense_variant | 3/47 | A2 | |||
SMCHD1 | ENST00000684915.1 | n.567G>A | non_coding_transcript_exon_variant | 3/14 |
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
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2012 | - - |
Pathogenic, no assertion criteria provided | research | MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital | - | - - |
Facioscapulohumeral muscular dystrophy 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2012 | - - |
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
MutationTaster
Benign
D;D
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