chr10-68199581-G-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_032578.4(MYPN):c.3493+6G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000012 in 1,582,742 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 (no stars).
Frequency
Genomes: 𝑓 0.000025 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
MYPN
NM_032578.4 splice_donor_region, intron
NM_032578.4 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00003731
2
Clinical Significance
Conservation
PhyloP100: -0.162
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 -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
Variant 10-68199581-G-T is Benign according to our data. Variant chr10-68199581-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1284526.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-68199581-G-T is described in Lovd as [Likely_benign].
BS2
High AC in GnomAdExome4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.3493+6G>T | splice_donor_region_variant, intron_variant | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.3493+6G>T | splice_donor_region_variant, intron_variant | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000246 AC: 3AN: 121732Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000198 AC: 4AN: 201692Hom.: 0 AF XY: 0.0000369 AC XY: 4AN XY: 108544
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GnomAD4 exome AF: 0.0000110 AC: 16AN: 1461010Hom.: 0 Cov.: 40 AF XY: 0.0000110 AC XY: 8AN XY: 726846
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GnomAD4 genome AF: 0.0000246 AC: 3AN: 121732Hom.: 0 Cov.: 30 AF XY: 0.0000507 AC XY: 3AN XY: 59202
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at