rs104894806

Positions:

• chrX-154380979-C-A
• chrX-154380979-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

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).

• Frequency: Genomes: not found (cov: 24)
• Consequence: EMD NM_000117.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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	Protein	UniProt
EMD	NM_000117.3	c.547C>A	p.Pro183Thr	missense_variant	6/6	ENST00000369842.9	NP_000108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMD	ENST00000369842.9	c.547C>A	p.Pro183Thr	missense_variant	6/6	1	NM_000117.3	ENSP00000358857	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 24

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.55	D;T
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.0000017	A;A
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.53
Sift	Benign	0.32	T;T
Sift4G	Uncertain	0.035	D;D
Polyphen		0.99	D;.
Vest4		0.33
MutPred		0.52		Loss of glycosylation at P183 (P = 0.0662);.;
MVP		0.98
MPC		1.0
ClinPred		0.73	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs104894806; hg19: chrX-153609339;