rs74143030

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032578.4(MYPN):c.1399G>A(p.Glu467Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 1,610,680 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E467E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.040 ( 398 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 363 hom. )

Consequence

MYPN
NM_032578.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.69

Publications

10 publications found

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:

RN7SKP202 (HGNC:45926): (RN7SK pseudogene 202)

RN7SKP202 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025645792).

BP6

Variant 10-68158567-G-A is Benign according to our data. Variant chr10-68158567-G-A is described in ClinVar as Benign. ClinVar VariationId is 31827.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYPN	NM_032578.4	MANE Select	c.1399G>A	p.Glu467Lys	missense	Exon 7 of 20	NP_115967.2
MYPN	NM_001256267.2		c.1399G>A	p.Glu467Lys	missense	Exon 8 of 21	NP_001243196.1
MYPN	NM_001256268.2		c.517G>A	p.Glu173Lys	missense	Exon 11 of 24	NP_001243197.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYPN	ENST00000358913.10	TSL:1 MANE Select	c.1399G>A	p.Glu467Lys	missense	Exon 7 of 20	ENSP00000351790.5
MYPN	ENST00000540630.6	TSL:1	c.1453G>A	p.Glu485Lys	missense	Exon 7 of 20	ENSP00000441668.3
MYPN	ENST00000613327.5	TSL:1	c.1399G>A	p.Glu467Lys	missense	Exon 8 of 21	ENSP00000480757.2

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6072

AN:

152162

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0312

GnomAD2 exomes

AF:

0.0110

AC:

2755

AN:

251286

AF XY:

0.00797

show subpopulations

Gnomad AFR exome

AF:

0.144

Gnomad AMR exome

AF:

0.00897

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00767

GnomAD4 exome

AF:

0.00436

AC:

6364

AN:

1458400

Hom.:

363

Cov.:

AF XY:

0.00387

AC XY:

2812

AN XY:

725718

show subpopulations

African (AFR)

AF:

0.145

AC:

4847

AN:

33390

American (AMR)

AF:

0.0101

AC:

450

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.000336

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00921

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000371

AC:

411

AN:

1108860

Other (OTH)

AF:

0.00951

AC:

573

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

280

561

841

1122

1402

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

158

316

474

632

790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0399

AC:

6076

AN:

152280

Hom.:

398

Cov.:

AF XY:

0.0383

AC XY:

2851

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.137

AC:

5693

AN:

41536

American (AMR)

AF:

0.0176

AC:

270

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68028

Other (OTH)

AF:

0.0308

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

267

534

800

1067

1334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0162

Hom.:

309

Bravo

AF:

0.0461

ESP6500AA

AF:

0.144

AC:

636

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.0137

AC:

1657

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Dilated cardiomyopathy 1KK (3)

Cardiovascular phenotype (1)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

0.010

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.23

PhyloP100

7.7

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.29

REVEL

Benign

0.20

Sift

Benign

0.41

Sift4G

Benign

0.71

Polyphen

0.48

Vest4

0.38

MPC

0.18

ClinPred

0.017

GERP RS

4.8

Varity_R

0.23

gMVP

0.51

Mutation Taster

=91/9

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over