rs397515460
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_015896.4(ZMYND10):c.967C>T(p.Gln323Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000372 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ZMYND10
NM_015896.4 stop_gained
NM_015896.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
ZMYND10 (HGNC:19412): (zinc finger MYND-type containing 10) This gene encodes a protein containing a MYND-type zinc finger domain that likely functions in assembly of the dynein motor. Mutations in this gene can cause primary ciliary dyskinesia. This gene is also considered a tumor suppressor gene and is often mutated, deleted, or hypermethylated and silenced in cancer cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-50342047-G-A is Pathogenic according to our data. Variant chr3-50342047-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 66024.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMYND10 | NM_015896.4 | c.967C>T | p.Gln323Ter | stop_gained | 9/12 | ENST00000231749.8 | |
ZMYND10 | NM_001308379.2 | c.952C>T | p.Gln318Ter | stop_gained | 8/11 | ||
ZMYND10 | XM_005265216.4 | c.730C>T | p.Gln244Ter | stop_gained | 8/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMYND10 | ENST00000231749.8 | c.967C>T | p.Gln323Ter | stop_gained | 9/12 | 1 | NM_015896.4 | P1 | |
ZMYND10-AS1 | ENST00000440013.1 | n.123+819G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251378Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135886
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461844Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727224
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74390
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Primary ciliary dyskinesia 22 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 08, 2013 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
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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