10-68114347-C-CTT

Variant names:

• chr10-68114347-C-CTT
• rs200370503
• NM_032578.4:c.-2+4637_-2+4638dupTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032578.4(MYPN):​c.-2+4637_-2+4638dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.046 (376 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.627
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-68114347-C-CTT is Benign according to our data. Variant chr10-68114347-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 1190956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.-2+4637_-2+4638dupTT		intron_variant	Intron 1 of 19	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.-2+4624_-2+4625insTT		intron_variant	Intron 1 of 19	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6237 AN: 135516 Hom.: 376 Cov.: 0

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00465

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.0342

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0604

Gnomad MID AF: 0.0216

Gnomad NFE AF: 0.0345

Gnomad OTH AF: 0.0437

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

GnomAD4 genome AF: 0.0460 AC: 6236 AN: 135516 Hom.: 376 Cov.: 0 AF XY: 0.0522 AC XY: 3388 AN XY: 64890

African (AFR) AF: 0.0107 AC: 390 AN: 36514

American (AMR) AF: 0.0793 AC: 1053 AN: 13286

Ashkenazi Jewish (ASJ) AF: 0.0342 AC: 114 AN: 3332

East Asian (EAS) AF: 0.214 AC: 1004 AN: 4702

South Asian (SAS) AF: 0.227 AC: 976 AN: 4296

European-Finnish (FIN) AF: 0.0604 AC: 404 AN: 6690

Middle Eastern (MID) AF: 0.0236 AC: 6 AN: 254

European-Non Finnish (NFE) AF: 0.0345 AC: 2201 AN: 63742

Other (OTH) AF: 0.0457 AC: 84 AN: 1840

Alfa AF: 0.0199 Hom.: 138

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 19, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200370503; hg19: chr10-69874104;