rs144764983

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_032578.4(MYPN):c.1104C>T(p.Gly368Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,613,020 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

MYPN
NM_032578.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: 1.14

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=-0.27).

BP6

Variant 10-68145500-C-T is Benign according to our data. Variant chr10-68145500-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 31836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68145500-C-T is described in Lovd as [Benign]. Variant chr10-68145500-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00158 (241/152152) while in subpopulation NFE AF= 0.00298 (203/68008). AF 95% confidence interval is 0.00265. There are 1 homozygotes in gnomad4. There are 99 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4 link	c.1104C>T	p.Gly368Gly	synonymous_variant	Exon 4 of 20	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10 link	c.1104C>T	p.Gly368Gly	synonymous_variant	Exon 4 of 20	1	NM_032578.4	ENSP00000351790.5		Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.00159

AC:

241

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00298

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00149

AC:

374

AN:

251082

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135700

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00223

AC:

3264

AN:

1460868

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1590

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000919

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.00274

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00158

AC:

241

AN:

152152

Hom.:

Cov.:

AF XY:

0.00133

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.00298

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00234

Hom.:

Bravo

AF:

0.00186

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00365

EpiControl

AF:

0.00379

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Jan 13, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Gly368Gly in exon 5 of MYPN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.3% (30/8600) of E uropean American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs144764983). -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 22, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Oct 09, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1KK

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 28, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2Other:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYPN: BP4, BP7 -

Apr 27, 2012

Leiden Muscular Dystrophy (MYPN)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 19, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely 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

-0.27

CADD

Benign

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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