NM_032578.4:c.-1-150A>T

Variant names:

• chr10-68121288-A-T
• rs71578985
• NM_032578.4:c.-1-150A>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.-1-150A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 730,496 control chromosomes in the GnomAD database, including 5,683 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1192 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4491 hom.)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.151
• 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 10-68121288-A-T is Benign according to our data. Variant chr10-68121288-A-T is described in ClinVar as [Benign]. Clinvar id is 1241484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.-1-150A>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.-1-150A>T		intron_variant	Intron 1 of 19	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18542 AN: 152062 Hom.: 1187 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.114 AC: 65656 AN: 578316 Hom.: 4491 AF XY: 0.117 AC XY: 34706 AN XY: 296116

African (AFR) AF: 0.106 AC: 1569 AN: 14830

American (AMR) AF: 0.102 AC: 1675 AN: 16372

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2023 AN: 14118

East Asian (EAS) AF: 0.124 AC: 3785 AN: 30404

South Asian (SAS) AF: 0.207 AC: 8418 AN: 40694

European-Finnish (FIN) AF: 0.129 AC: 4170 AN: 32380

Middle Eastern (MID) AF: 0.173 AC: 372 AN: 2146

European-Non Finnish (NFE) AF: 0.101 AC: 40136 AN: 397916

Other (OTH) AF: 0.119 AC: 3508 AN: 29456

GnomAD4 genome AF: 0.122 AC: 18564 AN: 152180 Hom.: 1192 Cov.: 32 AF XY: 0.123 AC XY: 9154 AN XY: 74416

African (AFR) AF: 0.115 AC: 4762 AN: 41510

American (AMR) AF: 0.104 AC: 1590 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.120 AC: 623 AN: 5184

South Asian (SAS) AF: 0.214 AC: 1028 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8001 AN: 68012

Other (OTH) AF: 0.131 AC: 276 AN: 2110

Alfa AF: 0.116 Hom.: 123

Bravo AF: 0.118

Asia WGS AF: 0.140 AC: 486 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	2.5
DANN	Benign	0.61
PhyloP100		0.15
PromoterAI		-0.018	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: rs71578985; hg19: chr10-69881045;