rs371661299

Variant names:

• chrX-154379541-C-T
• rs371661299
• NM_000117.3:c.57C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_000117.3(EMD):​c.57C>T​(p.Tyr19Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,169,490 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 26)
  • Exomes 𝑓: 0.0000028 (0 hom. 1 hem.)
• Consequence: EMD NM_000117.3 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0730
• Publications: 1 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• heart conduction disease

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

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant X-154379541-C-T is Benign according to our data. Variant chrX-154379541-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 227354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.073 with no splicing effect.

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.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 6	NP_000108.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMD	ENST00000369842.9	TSL:1 MANE Select	c.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 6	ENSP00000358857.4
	EMD	ENST00000933532.1		c.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 6	ENSP00000603591.1
	EMD	ENST00000933533.1		c.57C>T	p.Tyr19Tyr	synonymous	Exon 1 of 6	ENSP00000603592.1

Frequencies

GnomAD3 genomes AF: 0.00000884 AC: 1 AN: 113105 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000320

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000854 AC: 1 AN: 117140 AF XY: 0.0000251

Gnomad AFR exome AF: 0.000135

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 3 AN: 1056385 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 1 AN XY: 345117

African (AFR) AF: 0.000119 AC: 3 AN: 25143

American (AMR) AF: 0.00 AC: 0 AN: 28717

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18651

East Asian (EAS) AF: 0.00 AC: 0 AN: 27420

South Asian (SAS) AF: 0.00 AC: 0 AN: 50234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4069

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 820838

Other (OTH) AF: 0.00 AC: 0 AN: 44465

GnomAD4 genome AF: 0.00000884 AC: 1 AN: 113105 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 35259

African (AFR) AF: 0.0000320 AC: 1 AN: 31250

American (AMR) AF: 0.00 AC: 0 AN: 10825

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3577

South Asian (SAS) AF: 0.00 AC: 0 AN: 2851

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53240

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)
-	-	1	X-linked Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.93
PhyloP100		-0.073
PromoterAI		-0.026	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs371661299; hg19: chrX-153607901;