chr10-68207690-G-A

Variant names:

• chr10-68207690-G-A
• rs6480314
• NM_032578.4:c.3793+787G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032578.4(MYPN):​c.3793+787G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,180 control chromosomes in the GnomAD database, including 53,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53491 hom., cov: 33)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• Publications: 16 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LOC124902443 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.889 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYPN	NM_032578.4	MANE Select	c.3793+787G>A		intron	N/A	NP_115967.2
	MYPN	NM_001256267.2		c.3793+787G>A		intron	N/A	NP_001243196.1
	MYPN	NM_001256268.2		c.2911+787G>A		intron	N/A	NP_001243197.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYPN	ENST00000358913.10	TSL:1 MANE Select	c.3793+787G>A		intron	N/A	ENSP00000351790.5
	MYPN	ENST00000540630.6	TSL:1	c.3847+787G>A		intron	N/A	ENSP00000441668.3
	MYPN	ENST00000613327.5	TSL:1	c.3793+787G>A		intron	N/A	ENSP00000480757.2

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127192 AN: 152060 Hom.: 53447 Cov.: 33

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.723

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.835

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.836 AC: 127288 AN: 152180 Hom.: 53491 Cov.: 33 AF XY: 0.834 AC XY: 62015 AN XY: 74376

African (AFR) AF: 0.897 AC: 37230 AN: 41526

American (AMR) AF: 0.789 AC: 12057 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 2510 AN: 3472

East Asian (EAS) AF: 0.869 AC: 4508 AN: 5186

South Asian (SAS) AF: 0.801 AC: 3866 AN: 4826

European-Finnish (FIN) AF: 0.793 AC: 8375 AN: 10562

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56111 AN: 68008

Other (OTH) AF: 0.837 AC: 1762 AN: 2106

Alfa AF: 0.828 Hom.: 108028

Bravo AF: 0.837

Asia WGS AF: 0.839 AC: 2917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.53
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6480314; hg19: chr10-69967447;