X-154379690-G-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM5PP3BS2

The NM_000117.3(EMD):ā€‹c.83G>Cā€‹(p.Gly28Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000547 in 1,096,038 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G28R) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 25)
Exomes š‘“: 0.0000055 ( 0 hom. 3 hem. )

Consequence

EMD
NM_000117.3 missense, splice_region

Scores

4
7
6
Splicing: ADA: 0.9678
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.67
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM5
Other missense variant is known to change same aminoacid residue: Variant chrX-154379566-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 425517.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=2, Uncertain_significance=1}.
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EMDNM_000117.3 linkuse as main transcriptc.83G>C p.Gly28Ala missense_variant, splice_region_variant 2/6 ENST00000369842.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EMDENST00000369842.9 linkuse as main transcriptc.83G>C p.Gly28Ala missense_variant, splice_region_variant 2/61 NM_000117.3 P1

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD3 exomes
AF:
0.00000578
AC:
1
AN:
173152
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
64462
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
6
AN:
1096038
Hom.:
0
Cov.:
31
AF XY:
0.00000828
AC XY:
3
AN XY:
362336
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000713
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
25
ExAC
AF:
0.00000832
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.47
T
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.68
T
M_CAP
Pathogenic
0.79
D
MetaRNN
Pathogenic
0.86
D
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.61
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.33
Sift
Uncertain
0.0070
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.48
MutPred
0.81
Loss of loop (P = 0.1242);
MVP
0.67
MPC
1.0
ClinPred
0.60
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.61
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.97
dbscSNV1_RF
Pathogenic
0.82
SpliceAI score (max)
0.13
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs781978021; hg19: chrX-153608050; API