10-68121325-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032578.4(MYPN):c.-1-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 878,230 control chromosomes in the GnomAD database, including 5,523 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (652 hom., cov: 33)
  • Exomes 𝑓: 0.11 (4871 hom.)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0500

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-68121325-C-T is Benign according to our data. Variant chr10-68121325-C-T is described in ClinVar as [Benign]. Clinvar id is 1280430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYPN	NM_032578.4	c.-1-113C>T		intron_variant		ENST00000358913.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYPN	ENST00000358913.10	c.-1-113C>T		intron_variant		1	NM_032578.4	P1

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12647 AN: 152060 Hom.: 651 Cov.: 33

Gnomad AFR AF: 0.0301

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.0860

GnomAD4 exome AF: 0.110 AC: 80179 AN: 726052 Hom.: 4871 AF XY: 0.110 AC XY: 40638 AN XY: 369678

Gnomad4 AFR exome AF: 0.0267

Gnomad4 AMR exome AF: 0.0581

Gnomad4 ASJ exome AF: 0.0681

Gnomad4 EAS exome AF: 0.0746

Gnomad4 SAS exome AF: 0.0771

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.0941

GnomAD4 genome AF: 0.0831 AC: 12643 AN: 152178 Hom.: 652 Cov.: 33 AF XY: 0.0802 AC XY: 5967 AN XY: 74408

Gnomad4 AFR AF: 0.0301

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.0712

Gnomad4 EAS AF: 0.0540

Gnomad4 SAS AF: 0.0632

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.0842

Alfa AF: 0.103 Hom.: 117

Bravo AF: 0.0799

Asia WGS AF: 0.0560 AC: 196 AN: 3478

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

Jun 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.4
Dann	Benign	0.62

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: rs56355961; hg19: chr10-69881082;