rs151074632

Variant names:

• chrX-154380927-G-A
• rs151074632
• NM_000117.3:c.495G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-154380927-G-A
• chrX-154380927-G-T
• chrX-154380927-G-C

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.495G>A​(p.Thr165Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,209,810 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 458 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T165T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., 25 hem., cov: 24)
  • Exomes 𝑓: 0.0013 (0 hom. 433 hem.)
• Consequence: EMD NM_000117.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18
• Conservation: PhyloP100: -1.19
• 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=-0.6).
• BP6: Variant X-154380927-G-A is Benign according to our data. Variant chrX-154380927-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 42276.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000796 (89/111845) while in subpopulation NFE AF = 0.0014 (74/52944). AF 95% confidence interval is 0.00114. There are 0 homozygotes in GnomAd4. There are 25 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 25 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.495G>A	p.Thr165Thr	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.495G>A	p.Thr165Thr	synonymous	Exon 6 of 6	ENSP00000358857.4	P50402
	EMD	ENST00000933532.1		c.522G>A	p.Thr174Thr	synonymous	Exon 6 of 6	ENSP00000603591.1
	EMD	ENST00000933533.1		c.519G>A	p.Thr173Thr	synonymous	Exon 6 of 6	ENSP00000603592.1

Frequencies

GnomAD3 genomes AF: 0.000787 AC: 88 AN: 111794 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000358

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000937

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000736

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000514 AC: 94 AN: 182896 AF XY: 0.000578

Gnomad AFR exome AF: 0.000304

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000637

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00126 AC: 1382 AN: 1097965 Hom.: 0 Cov.: 32 AF XY: 0.00119 AC XY: 433 AN XY: 363365

African (AFR) AF: 0.000151 AC: 4 AN: 26403

American (AMR) AF: 0.0000568 AC: 2 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000369 AC: 2 AN: 54149

European-Finnish (FIN) AF: 0.0000497 AC: 2 AN: 40243

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

European-Non Finnish (NFE) AF: 0.00159 AC: 1337 AN: 842142

Other (OTH) AF: 0.000738 AC: 34 AN: 46094

GnomAD4 genome AF: 0.000796 AC: 89 AN: 111845 Hom.: 0 Cov.: 24 AF XY: 0.000734 AC XY: 25 AN XY: 34039

African (AFR) AF: 0.000357 AC: 11 AN: 30821

American (AMR) AF: 0.0000936 AC: 1 AN: 10685

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3532

South Asian (SAS) AF: 0.00111 AC: 3 AN: 2710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6091

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

European-Non Finnish (NFE) AF: 0.00140 AC: 74 AN: 52944

Other (OTH) AF: 0.00 AC: 0 AN: 1519

Alfa AF: 0.000182 Hom.: 1

Bravo AF: 0.000642

EpiCase AF: 0.000818

EpiControl AF: 0.00130

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	5	not provided (5)
-	-	2	X-linked Emery-Dreifuss muscular dystrophy (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	EMD-related disorder (1)
-	-	1	Emery-Dreifuss muscular dystrophy (1)
-	-	1	Emery-Dreifuss muscular dystrophy 1, X-linked (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs151074632; hg19: chrX-153609287; COSMIC: COSV100877352; COSMIC: COSV100877352;