10-68158164-C-T

Variant names:

• chr10-68158164-C-T
• rs2176105
• NM_032578.4:c.1318-322C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032578.4(MYPN):​c.1318-322C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 268,854 control chromosomes in the GnomAD database, including 78,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45575 hom., cov: 30)
  • Exomes 𝑓: 0.74 (32754 hom.)
• Consequence: MYPN NM_032578.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.331

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]

RN7SKP202 (HGNC:45926): (RN7SK pseudogene 202)

LOC107984240 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 10-68158164-C-T is Benign according to our data. Variant chr10-68158164-C-T is described in ClinVar as [Benign]. Clinvar id is 683654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYPN	NM_032578.4	c.1318-322C>T		intron_variant	Intron 6 of 19	ENST00000358913.10	NP_115967.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYPN	ENST00000358913.10	c.1318-322C>T		intron_variant	Intron 6 of 19	1	NM_032578.4	ENSP00000351790.5

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116317 AN: 151340 Hom.: 45522 Cov.: 30

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.746

GnomAD4 exome AF: 0.736 AC: 86463 AN: 117398 Hom.: 32754 Cov.: 0 AF XY: 0.731 AC XY: 44822 AN XY: 61292

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.734

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.686

Gnomad4 FIN exome AF: 0.790

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.748

GnomAD4 genome AF: 0.769 AC: 116426 AN: 151456 Hom.: 45575 Cov.: 30 AF XY: 0.765 AC XY: 56574 AN XY: 73988

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.743

Alfa AF: 0.779 Hom.: 5432

Bravo AF: 0.768

Asia WGS AF: 0.497 AC: 1729 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.38

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: rs2176105; hg19: chr10-69917921;