chrX-154380897-C-T

Variant names:

• chrX-154380897-C-T
• rs143447675
• NM_000117.3:c.465C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000117.3(EMD):​c.465C>T​(p.Tyr155Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000721 in 1,210,507 control chromosomes in the GnomAD database, including 3 homozygotes. There are 245 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (2 hom., 121 hem., cov: 24)
  • Exomes 𝑓: 0.00042 (1 hom. 124 hem.)
• Consequence: EMD NM_000117.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -1.31
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• heart conduction disease

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant X-154380897-C-T is Benign according to our data. Variant chrX-154380897-C-T is described in ClinVar as Benign. ClinVar VariationId is 42274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.31 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00371 (417/112464) while in subpopulation AFR AF = 0.0125 (389/31026). AF 95% confidence interval is 0.0115. There are 2 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

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.465C>T	p.Tyr155Tyr	synonymous	Exon 6 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.465C>T	p.Tyr155Tyr	synonymous	Exon 6 of 6	ENSP00000358857.4	P50402
	EMD	ENST00000933532.1		c.492C>T	p.Tyr164Tyr	synonymous	Exon 6 of 6	ENSP00000603591.1
	EMD	ENST00000933533.1		c.489C>T	p.Tyr163Tyr	synonymous	Exon 6 of 6	ENSP00000603592.1

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 417 AN: 112412 Hom.: 2 Cov.: 24

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00204

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: 0.0000377

Gnomad OTH AF: 0.00264

GnomAD2 exomes AF: 0.00112 AC: 205 AN: 183035 AF XY: 0.000754

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000612

Gnomad OTH exome AF: 0.00111

GnomAD4 exome AF: 0.000415 AC: 456 AN: 1098043 Hom.: 1 Cov.: 32 AF XY: 0.000341 AC XY: 124 AN XY: 363443

African (AFR) AF: 0.0112 AC: 297 AN: 26403

American (AMR) AF: 0.00134 AC: 47 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19385

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40332

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4137

European-Non Finnish (NFE) AF: 0.0000712 AC: 60 AN: 842131

Other (OTH) AF: 0.00111 AC: 51 AN: 46094

GnomAD4 genome AF: 0.00371 AC: 417 AN: 112464 Hom.: 2 Cov.: 24 AF XY: 0.00349 AC XY: 121 AN XY: 34624

African (AFR) AF: 0.0125 AC: 389 AN: 31026

American (AMR) AF: 0.00204 AC: 22 AN: 10774

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2729

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53091

Other (OTH) AF: 0.00260 AC: 4 AN: 1536

Alfa AF: 0.00203 Hom.: 11

Bravo AF: 0.00484

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	9	not specified (9)
-	-	1	Cardiomyopathy (1)
-	-	1	Emery-Dreifuss muscular dystrophy 1, X-linked (1)
-	-	1	not provided (1)
-	-	1	X-linked Emery-Dreifuss muscular dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.25
DANN	Benign	0.37
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs143447675; hg19: chrX-153609257; COSMIC: COSV100877370; COSMIC: COSV100877370;