10-68121325-C-T

Variant names:

• chr10-68121325-C-T
• rs56355961
• NM_032578.4:c.-1-113C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032578.4(MYPN):​c.-1-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 878,230 control chromosomes in the GnomAD database, including 5,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (652 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4871 hom.)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-68121325-C-T is Benign according to our data. Variant chr10-68121325-C-T is described in ClinVar as [Benign]. Clinvar id is 1280430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.-1-113C>T		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.-1-113C>T		intron_variant	Intron 1 of 19	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12647 AN: 152060 Hom.: 651 Cov.: 33

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0860

GnomAD4 exome AF: 0.110 AC: 80179 AN: 726052 Hom.: 4871 AF XY: 0.110 AC XY: 40638 AN XY: 369678

African (AFR) AF: 0.0267 AC: 458 AN: 17152

American (AMR) AF: 0.0581 AC: 1218 AN: 20978

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 1068 AN: 15694

East Asian (EAS) AF: 0.0746 AC: 2428 AN: 32540

South Asian (SAS) AF: 0.0771 AC: 3630 AN: 47104

European-Finnish (FIN) AF: 0.0756 AC: 3298 AN: 43616

Middle Eastern (MID) AF: 0.0648 AC: 159 AN: 2452

European-Non Finnish (NFE) AF: 0.126 AC: 64674 AN: 512028

Other (OTH) AF: 0.0941 AC: 3246 AN: 34488

GnomAD4 genome AF: 0.0831 AC: 12643 AN: 152178 Hom.: 652 Cov.: 33 AF XY: 0.0802 AC XY: 5967 AN XY: 74408

African (AFR) AF: 0.0301 AC: 1250 AN: 41530

American (AMR) AF: 0.0616 AC: 942 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.0540 AC: 280 AN: 5186

South Asian (SAS) AF: 0.0632 AC: 304 AN: 4812

European-Finnish (FIN) AF: 0.0674 AC: 713 AN: 10584

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8500 AN: 67988

Other (OTH) AF: 0.0842 AC: 178 AN: 2114

Alfa AF: 0.112 Hom.: 1419

Bravo AF: 0.0799

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.4
DANN	Benign	0.62
PhyloP100		-0.050
PromoterAI		-0.022	Neutral
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: rs56355961; hg19: chr10-69881082;