chr10-68114347-C-CT

Position:

• chr10-68114347-C-CT

Variant summary

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

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

• Frequency:
  • Genomes: 𝑓 0.30 (6730 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: 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-CT is Benign according to our data. Variant chr10-68114347-C-CT is described in ClinVar as [Benign]. Clinvar id is 1291626.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.299 AC: 40438 AN: 135452 Hom.: 6717 Cov.: 0

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.333

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.299 AC: 40460 AN: 135452 Hom.: 6730 Cov.: 0 AF XY: 0.299 AC XY: 19379 AN XY: 64870

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.289

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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;