10-68121346-A-T

Variant names:

• chr10-68121346-A-T
• rs10509295
• NM_032578.4:c.-1-92A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032578.4(MYPN):​c.-1-92A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,087,788 control chromosomes in the GnomAD database, including 9,596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1956 hom., cov: 33)
  • Exomes 𝑓: 0.12 (7640 hom.)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.915
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-68121346-A-T is Benign according to our data. Variant chr10-68121346-A-T is described in ClinVar as [Benign]. Clinvar id is 1268364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.-1-92A>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.-1-92A>T		intron_variant	Intron 1 of 19	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22622 AN: 152150 Hom.: 1950 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.122 AC: 114064 AN: 935520 Hom.: 7640 AF XY: 0.123 AC XY: 58263 AN XY: 471852

African (AFR) AF: 0.238 AC: 5115 AN: 21478

American (AMR) AF: 0.0944 AC: 2454 AN: 26008

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 2477 AN: 17650

East Asian (EAS) AF: 0.0311 AC: 1113 AN: 35750

South Asian (SAS) AF: 0.173 AC: 9587 AN: 55536

European-Finnish (FIN) AF: 0.115 AC: 5522 AN: 48152

Middle Eastern (MID) AF: 0.190 AC: 555 AN: 2914

European-Non Finnish (NFE) AF: 0.119 AC: 81904 AN: 686346

Other (OTH) AF: 0.128 AC: 5337 AN: 41686

GnomAD4 genome AF: 0.149 AC: 22649 AN: 152268 Hom.: 1956 Cov.: 33 AF XY: 0.146 AC XY: 10908 AN XY: 74464

African (AFR) AF: 0.236 AC: 9809 AN: 41542

American (AMR) AF: 0.106 AC: 1627 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3468

East Asian (EAS) AF: 0.0250 AC: 130 AN: 5192

South Asian (SAS) AF: 0.178 AC: 857 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10592

Middle Eastern (MID) AF: 0.175 AC: 51 AN: 292

European-Non Finnish (NFE) AF: 0.117 AC: 7973 AN: 68020

Other (OTH) AF: 0.161 AC: 340 AN: 2116

Alfa AF: 0.132 Hom.: 176

Bravo AF: 0.153

Asia WGS AF: 0.0900 AC: 311 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 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	-0.86
CADD	Benign	7.1
DANN	Benign	0.38
PhyloP100		0.92
PromoterAI		-0.0030	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: rs10509295; hg19: chr10-69881103;