10-68114347-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_032578.4(MYPN):c.-2+4637_-2+4638dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYPN	NM_032578.4	c.-2+4637_-2+4638dup		intron_variant		ENST00000358913.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYPN	ENST00000358913.10	c.-2+4637_-2+4638dup		intron_variant		1	NM_032578.4	P1

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

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.0342

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0604

Gnomad4 NFE AF: 0.0345

Gnomad4 OTH AF: 0.0457

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 19, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200370503; hg19: chr10-69874104;