rs1064797096
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5
The NM_005219.5(DIAPH1):c.3624_3625delAG(p.Ala1210fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
DIAPH1
NM_005219.5 frameshift
NM_005219.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.20
Genes affected
DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0511 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-141524178-CCT-C is Pathogenic according to our data. Variant chr5-141524178-CCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 424874.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-141524178-CCT-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIAPH1 | NM_005219.5 | c.3624_3625delAG | p.Ala1210fs | frameshift_variant | 27/28 | ENST00000389054.8 | NP_005210.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.3624_3625delAG | p.Ala1210fs | frameshift_variant | 27/28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.3597_3598delAG | p.Ala1201fs | frameshift_variant | 26/27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000647433.1 | c.3624_3625delAG | p.Ala1210fs | frameshift_variant | 27/29 | ENSP00000494675.1 | ||||
DIAPH1 | ENST00000468119.3 | c.30_31delAG | p.Ala12fs | frameshift_variant | 2/3 | 4 | ENSP00000493546.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 20, 2017 | - - |
Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at