MYPN p.Ser803Arg

Variant names:

• chr10-68174499-A-C
• rs1479692619
• NM_032578.4:c.2407A>C
• MYPN p.Ser803Arg

Your query was ambiguous. Multiple possible variants found:

• chr10-68174499-A-C
• chr10-68174501-C-A
• chr10-68174501-C-G
• chr10-68174499-AGC-CGT
• chr10-68174499-AGC-CGA
• chr10-68174499-AGC-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032578.4(MYPN):​c.2407A>C​(p.Ser803Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S803N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYPN NM_032578.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18441314).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYPN	NM_032578.4	MANE Select	c.2407A>C	p.Ser803Arg	missense	Exon 11 of 20	NP_115967.2	Q86TC9-1
	MYPN	NM_001256267.2		c.2407A>C	p.Ser803Arg	missense	Exon 12 of 21	NP_001243196.1	Q86TC9-1
	MYPN	NM_001256268.2		c.1525A>C	p.Ser509Arg	missense	Exon 15 of 24	NP_001243197.1	A0A087WX60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYPN	ENST00000358913.10	TSL:1 MANE Select	c.2407A>C	p.Ser803Arg	missense	Exon 11 of 20	ENSP00000351790.5	Q86TC9-1
	MYPN	ENST00000540630.6	TSL:1	c.2461A>C	p.Ser821Arg	missense	Exon 11 of 20	ENSP00000441668.3	A0A8J9ASZ5
	MYPN	ENST00000613327.5	TSL:1	c.2407A>C	p.Ser803Arg	missense	Exon 12 of 21	ENSP00000480757.2	Q86TC9-1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251184 AF XY: 0.00

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461768 Hom.: 0 Cov.: 74 AF XY: 0.00 AC XY: 0 AN XY: 727160

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111922

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152070 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74296

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.079
Sift	Uncertain	0.020	D
Sift4G	Benign	0.34	T
Varity_R		0.20
gMVP		0.31
Mutation Taster		=86/14	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1479692619;

hg19: chr10-69934256;