rs756608855
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_Very_StrongBP7BS2_Supporting
The NM_005219.5(DIAPH1):c.2373C>T(p.Asp791=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,450 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: not found (cov: 32)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
DIAPH1
NM_005219.5 synonymous
NM_005219.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.300
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 5-141572026-G-A is Benign according to our data. Variant chr5-141572026-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 227303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.3 with no splicing effect.
BS2
High AC in GnomAdExome4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIAPH1 | NM_005219.5 | c.2373C>T | p.Asp791= | synonymous_variant | 17/28 | ENST00000389054.8 | NP_005210.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.2373C>T | p.Asp791= | synonymous_variant | 17/28 | 5 | NM_005219.5 | ENSP00000373706 | A2 | |
DIAPH1 | ENST00000518047.5 | c.2346C>T | p.Asp782= | synonymous_variant | 16/27 | 5 | ENSP00000428268 | P4 | ||
DIAPH1 | ENST00000647433.1 | c.2373C>T | p.Asp791= | synonymous_variant | 17/29 | ENSP00000494675 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249570Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135404
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461450Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727078
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 30, 2015 | p.Asp791Asp in exon 17 of DIAPH1: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 2/11566 of Latin o chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs756608855). - |
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 11, 2023 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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