rs104894806
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP5
The NM_000117.3(EMD):c.547C>A(p.Pro183Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P183L) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 24)
Consequence
EMD
NM_000117.3 missense
NM_000117.3 missense
Scores
1
8
8
Clinical Significance
Conservation
PhyloP100: 1.15
Genes affected
EMD (HGNC:3331): (emerin) Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Dreifuss-Emery muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the emerin gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a region_of_interest Interaction with CTNNB1 (size 18) in uniprot entity EMD_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_000117.3
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrX-154380980-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11178.Status of the report is criteria_provided_single_submitter, 1 stars.
PP5
?
Variant X-154380979-C-A is Pathogenic according to our data. Variant chrX-154380979-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 11179.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154380979-C-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EMD | NM_000117.3 | c.547C>A | p.Pro183Thr | missense_variant | 6/6 | ENST00000369842.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EMD | ENST00000369842.9 | c.547C>A | p.Pro183Thr | missense_variant | 6/6 | 1 | NM_000117.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
X-linked Emery-Dreifuss muscular dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.
MutationTaster
Benign
A;A
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Loss of glycosylation at P183 (P = 0.0662);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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