chr10-68166568-C-T

Position:

chr10-68166568-C-T

Variant summary

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

The NM_032578.4(MYPN):c.1875C>T(p.Pro625=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,613,890 control chromosomes in the GnomAD database, including 26,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2468 hom., cov: 31)

Exomes 𝑓: 0.18 ( 24159 hom. )

Consequence

MYPN
NM_032578.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -2.56

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 10-68166568-C-T is Benign according to our data. Variant chr10-68166568-C-T is described in ClinVar as [Benign]. Clinvar id is 31796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68166568-C-T is described in Lovd as [Benign]. Variant chr10-68166568-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.56 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.197 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.1875C>T	p.Pro625=	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.1875C>T	p.Pro625=	synonymous_variant	10/20	1	NM_032578.4	ENSP00000351790	P1	Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26371

AN:

151958

Hom.:

2457

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.0923

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.187

GnomAD3 exomes

AF:

0.188

AC:

47270

AN:

251328

Hom.:

4857

AF XY:

0.187

AC XY:

25423

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.154

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.0915

Gnomad SAS exome

AF:

0.191

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.177

AC:

259468

AN:

1461812

Hom.:

24159

Cov.:

AF XY:

0.178

AC XY:

129645

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.157

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.312

Gnomad4 EAS exome

AF:

0.0927

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.173

Gnomad4 OTH exome

AF:

0.179

GnomAD4 genome

AF:

0.174

AC:

26413

AN:

152078

Hom.:

2468

Cov.:

AF XY:

0.175

AC XY:

13002

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.0923

Gnomad4 SAS

AF:

0.178

Gnomad4 FIN

AF:

0.200

Gnomad4 NFE

AF:

0.173

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.167

Hom.:

1028

Bravo

AF:

0.177

Asia WGS

AF:

0.141

AC:

491

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 29, 2014	p.Pro625Pro in exon 11 of MYPN: This variant is not expected to have clinical si gnificance because it has been identified in 19% (1605/8600) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs2673793). -
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	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	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 09, 2023	- -

not provided

Benign:1Other:1

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

Dilated cardiomyopathy 1KK

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

-0.76

CADD

Benign

0.24

DANN

Benign

0.32

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