rs751087472
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_032578.4(MYPN):c.1851G>A(p.Val617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000074 ( 0 hom. )
Consequence
MYPN
NM_032578.4 synonymous
NM_032578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.506
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 10-68166544-G-A is Benign according to our data. Variant chr10-68166544-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.506 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000739 (108/1461884) while in subpopulation AMR AF= 0.000246 (11/44724). AF 95% confidence interval is 0.000137. There are 0 homozygotes in gnomad4_exome. There are 51 alleles in male gnomad4_exome subpopulation. Median coverage is 79. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 108 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.1851G>A | p.Val617= | synonymous_variant | 10/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.1851G>A | p.Val617= | synonymous_variant | 10/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251418Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135884
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461884Hom.: 0 Cov.: 79 AF XY: 0.0000701 AC XY: 51AN XY: 727244
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2020 | - - |
Dilated cardiomyopathy 1KK Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 26, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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