rs375320760
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_032578.4(MYPN):c.2703+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,613,748 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 1 hom. )
Consequence
MYPN
NM_032578.4 intron
NM_032578.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.440
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
Variant 10-68175474-G-A is Benign according to our data. Variant chr10-68175474-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68175474-G-A is described in Lovd as [Benign]. Variant chr10-68175474-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000572 (87/152216) while in subpopulation AFR AF= 0.00207 (86/41464). AF 95% confidence interval is 0.00172. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 87 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.2703+13G>A | intron_variant | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.2703+13G>A | intron_variant | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000572 AC: 87AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000119 AC: 30AN: 251314Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135820
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GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461532Hom.: 1 Cov.: 39 AF XY: 0.0000688 AC XY: 50AN XY: 727094
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GnomAD4 genome ? AF: 0.000572 AC: 87AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000444 AC XY: 33AN XY: 74366
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 23, 2015 | c.2703+13G>A in intron 13 of MYPN: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 0.1% (12/10398) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3753 20760). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Dilated cardiomyopathy 1KK Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | May 31, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at