rs71584491

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_032578.4(MYPN):c.2163C>A(p.Ala721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,613,986 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 303 hom., cov: 31)

Exomes 𝑓: 0.016 ( 458 hom. )

Consequence

MYPN
NM_032578.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.687

Variant links:

Genes affected

MYPN (HGNC:23246): (myopalladin) Striated muscle in vertebrates comprises large proteins which must be organized properly to contract efficiently. Z-lines in striated muscle are a sign of this organization, representing the ends of actin thin filaments, titin, nebulin or nebulette and accessory proteins required for structure and function. This gene encodes a protein which interacts with nebulin in skeletal muscle or nebulette in cardiac muscle and alpha-actinin. In addition, this gene product can interact with a protein with the I-band indicating it has a regulatory as well as structural function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]

MYPN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 10-68174255-C-A is Benign according to our data. Variant chr10-68174255-C-A is described in ClinVar as [Benign]. Clinvar id is 31806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68174255-C-A is described in Lovd as [Benign]. Variant chr10-68174255-C-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.687 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYPN	NM_032578.4 linkuse as main transcript	c.2163C>A	p.Ala721=	synonymous_variant	11/20	ENST00000358913.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYPN	ENST00000358913.10 linkuse as main transcript	c.2163C>A	p.Ala721=	synonymous_variant	11/20	1	NM_032578.4	P1	Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6132

AN:

151982

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0193

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0261

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0217

AC:

5445

AN:

251444

Hom.:

141

AF XY:

0.0212

AC XY:

2887

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0329

Gnomad FIN exome

AF:

0.0111

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0163

AC:

23776

AN:

1461886

Hom.:

458

Cov.:

AF XY:

0.0167

AC XY:

12127

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0182

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0332

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.0222

GnomAD4 genome

AF:

0.0405

AC:

6162

AN:

152100

Hom.:

303

Cov.:

AF XY:

0.0396

AC XY:

2944

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.0139

Gnomad4 OTH

AF:

0.0350

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0445

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0146

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Ala721Ala in exon 12 of MYPN: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 10.4% (458/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs71584491). -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 17, 2023	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 13, 2016	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Dilated cardiomyopathy 1KK

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 19, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Other:1

not provided, no classification provided

curation

Leiden Muscular Dystrophy (MYPN)

Apr 27, 2012

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

Cadd

Benign

9.6

Dann

Benign

0.78

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over