chrX-154379724-CGAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCCC-CG

Variant names:

• chrX-154379724-CGAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC-CG
• NM_000117.3:c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_000117.3(EMD):​c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC​(p.Glu40_Pro51delinsAla) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: EMD NM_000117.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35
• Publications: 0 publications found

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]

EMD Gene-Disease associations (from GenCC):

• X-linked Emery-Dreifuss muscular dystrophy

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• heart conduction disease

  Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_000117.3.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000117.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMD	NM_000117.3	MANE Select	c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC	p.Glu40_Pro51delinsAla	disruptive_inframe_deletion	Exon 2 of 6	NP_000108.1	P50402

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMD	ENST00000369842.9	TSL:1 MANE Select	c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC	p.Glu40_Pro51delinsAla	disruptive_inframe_deletion	Exon 2 of 6	ENSP00000358857.4	P50402
	EMD	ENST00000933532.1		c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC	p.Glu40_Pro51delinsAla	disruptive_inframe_deletion	Exon 2 of 6	ENSP00000603591.1
	EMD	ENST00000933533.1		c.119_151delAGTACGAGACCCAGAGGCGGCGGCTCTCGCCCC	p.Glu40_Pro51delinsAla	disruptive_inframe_deletion	Exon 2 of 6	ENSP00000603592.1

Frequencies

GnomAD3 genomes Cov.: 25

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-153608084;