X-154380944-C-T

Variant names:

• chrX-154380944-C-T
• NM_000117.3:c.512C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000117.3(EMD):​c.512C>T​(p.Ser171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,098,006 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: EMD NM_000117.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity EMD_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23348048).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMD	NM_000117.3	c.512C>T	p.Ser171Leu	missense_variant	Exon 6 of 6	ENST00000369842.9	NP_000108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMD	ENST00000369842.9	c.512C>T	p.Ser171Leu	missense_variant	Exon 6 of 6	1	NM_000117.3	ENSP00000358857.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098006 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363392

Gnomad4 AFR exome AF: 0.0000379

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D;T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.7	N;D
REVEL	Benign	0.24
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.81	P;.
Vest4		0.23
MutPred		0.32		Loss of phosphorylation at S171 (P = 0.0031);.;
MVP		0.73
MPC		0.57
ClinPred		0.79	D
GERP RS		4.2
Varity_R		0.14
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153609304;