dbSNP rs61854624: MYPN:p.Thr623Thr (chr10-68166562-C-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032578.4(MYPN):c.1869C>A(p.Thr623Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,976 control chromosomes in the GnomAD database, including 21,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1677 hom., cov: 31)

Exomes 𝑓: 0.16 ( 20185 hom. )

Consequence

MYPN
NM_032578.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0800

Publications

11 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 Gene-Disease associations (from GenCC):

MYPN-related myopathy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
cap myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
childhood-onset nemaline myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated restrictive cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
dilated cardiomyopathy 1KK
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYPN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 10-68166562-C-A is Benign according to our data. Variant chr10-68166562-C-A is described in ClinVar as Benign. ClinVar VariationId is 31803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 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	UniProt
MYPN	NM_032578.4	MANE Select	c.1869C>A	p.Thr623Thr	synonymous	Exon 10 of 20	NP_115967.2	Q86TC9-1
MYPN	NM_001256267.2		c.1869C>A	p.Thr623Thr	synonymous	Exon 11 of 21	NP_001243196.1	Q86TC9-1
MYPN	NM_001256268.2		c.987C>A	p.Thr329Thr	synonymous	Exon 14 of 24	NP_001243197.1	A0A087WX60

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYPN	ENST00000358913.10	TSL:1 MANE Select	c.1869C>A	p.Thr623Thr	synonymous	Exon 10 of 20	ENSP00000351790.5	Q86TC9-1
MYPN	ENST00000540630.6	TSL:1	c.1923C>A	p.Thr641Thr	synonymous	Exon 10 of 20	ENSP00000441668.3	A0A8J9ASZ5
MYPN	ENST00000613327.5	TSL:1	c.1869C>A	p.Thr623Thr	synonymous	Exon 11 of 21	ENSP00000480757.2	Q86TC9-1

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19639

AN:

152028

Hom.:

1672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.0926

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.150

GnomAD2 exomes

AF:

0.165

AC:

41580

AN:

251312

AF XY:

0.165

show subpopulations

Gnomad AFR exome

AF:

0.0295

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.0913

Gnomad FIN exome

AF:

0.184

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.161

AC:

234964

AN:

1461830

Hom.:

20185

Cov.:

AF XY:

0.161

AC XY:

117159

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0257

AC:

860

AN:

33480

American (AMR)

AF:

0.237

AC:

10585

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

7684

AN:

26136

East Asian (EAS)

AF:

0.0926

AC:

3676

AN:

39698

South Asian (SAS)

AF:

0.159

AC:

13741

AN:

86254

European-Finnish (FIN)

AF:

0.184

AC:

9845

AN:

53420

Middle Eastern (MID)

AF:

0.184

AC:

1063

AN:

5768

European-Non Finnish (NFE)

AF:

0.160

AC:

178078

AN:

1111964

Other (OTH)

AF:

0.156

AC:

9432

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

12403

24805

37208

49610

62013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6330

12660

18990

25320

31650

<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:

0.129

AC:

19660

AN:

152146

Hom.:

1677

Cov.:

AF XY:

0.132

AC XY:

9834

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0303

AC:

1259

AN:

41542

American (AMR)

AF:

0.185

AC:

2821

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1055

AN:

3472

East Asian (EAS)

AF:

0.0923

AC:

478

AN:

5180

South Asian (SAS)

AF:

0.152

AC:

731

AN:

4824

European-Finnish (FIN)

AF:

0.189

AC:

1995

AN:

10564

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10826

AN:

67970

Other (OTH)

AF:

0.149

AC:

315

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

847

1694

2541

3388

4235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.159

Hom.:

1135

Bravo

AF:

0.128

Asia WGS

AF:

0.125

AC:

435

AN:

3478

EpiCase

AF:

0.161

EpiControl

AF:

0.164

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Cardiovascular phenotype (1)

Dilated cardiomyopathy 1KK (1)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

(source)

DANN

Benign

0.28

PhyloP100

0.080

Mutation Taster

=98/2

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