rs58180147

Positions:

• chr10-68183877-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032578.4(MYPN):​c.2704-5028C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 152,102 control chromosomes in the GnomAD database, including 287 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.058 (287 hom., cov: 32)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYPN	NM_032578.4	c.2704-5028C>T		intron_variant		ENST00000358913.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYPN	ENST00000358913.10	c.2704-5028C>T		intron_variant		1	NM_032578.4	P1

Frequencies

GnomAD3 genomes AF: 0.0584 AC: 8871 AN: 151984 Hom.: 287 Cov.: 32

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0697

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00600

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0383

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

GnomAD4 genome AF: 0.0584 AC: 8877 AN: 152102 Hom.: 287 Cov.: 32 AF XY: 0.0556 AC XY: 4132 AN XY: 74364

Gnomad4 AFR AF: 0.0720

Gnomad4 AMR AF: 0.0699

Gnomad4 ASJ AF: 0.00893

Gnomad4 EAS AF: 0.00601

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0616

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0653 Hom.: 35

Bravo AF: 0.0629

Asia WGS AF: 0.0100 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs58180147; hg19: chr10-69943634;