10-68166340-T-C

Position:

chr10-68166340-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032578.4(MYPN):c.1647T>C(p.Ser549Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,613,676 control chromosomes in the GnomAD database, including 361,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27464 hom., cov: 30)

Exomes 𝑓: 0.67 ( 334390 hom. )

Consequence

MYPN
NM_032578.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.225

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:

MYPN (HGNC:):

MYPN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-68166340-T-C is Benign according to our data. Variant chr10-68166340-T-C is described in ClinVar as [Benign]. Clinvar id is 31795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68166340-T-C is described in Lovd as [Benign]. Variant chr10-68166340-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.225 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYPN	NM_032578.4 linkuse as main transcript	c.1647T>C	p.Ser549Ser	synonymous_variant	10/20	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10 linkuse as main transcript	c.1647T>C	p.Ser549Ser	synonymous_variant	10/20	1	NM_032578.4	ENSP00000351790.5		Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87767

AN:

151750

Hom.:

27445

Cov.:

show subpopulations

Gnomad AFR

AF:

0.350

Gnomad AMI

AF:

0.657

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.747

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.586

GnomAD3 exomes

AF:

0.631

AC:

158506

AN:

251378

Hom.:

52334

AF XY:

0.636

AC XY:

86387

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.341

Gnomad AMR exome

AF:

0.683

Gnomad ASJ exome

AF:

0.637

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.627

Gnomad FIN exome

AF:

0.739

Gnomad NFE exome

AF:

0.690

Gnomad OTH exome

AF:

0.640

GnomAD4 exome

AF:

0.671

AC:

980659

AN:

1461808

Hom.:

334390

Cov.:

AF XY:

0.671

AC XY:

487929

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.680

Gnomad4 ASJ exome

AF:

0.638

Gnomad4 EAS exome

AF:

0.332

Gnomad4 SAS exome

AF:

0.636

Gnomad4 FIN exome

AF:

0.737

Gnomad4 NFE exome

AF:

0.696

Gnomad4 OTH exome

AF:

0.629

GnomAD4 genome

AF:

0.578

AC:

87820

AN:

151868

Hom.:

27464

Cov.:

AF XY:

0.580

AC XY:

43008

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.350

Gnomad4 AMR

AF:

0.640

Gnomad4 ASJ

AF:

0.637

Gnomad4 EAS

AF:

0.304

Gnomad4 SAS

AF:

0.616

Gnomad4 FIN

AF:

0.747

Gnomad4 NFE

AF:

0.692

Gnomad4 OTH

AF:

0.584

Alfa

AF:

0.658

Hom.:

42911

Bravo

AF:

0.558

Asia WGS

AF:

0.446

AC:

1551

AN:

3478

EpiCase

AF:

0.682

EpiControl

AF:

0.674

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 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, criteria provided, single submitter	clinical testing	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	May 13, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 29, 2014	p.Ser549Ser in exon 11 of MYPN: This variant is not expected to have clinical si gnificance because it has been identified in 70% (5986/8600) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs2673794). -

Dilated cardiomyopathy 1KK

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:1Other:1

not provided, no classification provided	curation	Leiden Muscular Dystrophy (MYPN)	Apr 27, 2012	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

MYPN-related myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.5

DANN

Benign

0.56

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