rs189809247
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_005219.5(DIAPH1):c.1769G>T(p.Gly590Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,612,138 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G590D) has been classified as Uncertain significance.
Frequency
Consequence
NM_005219.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIAPH1 | NM_005219.5 | c.1769G>T | p.Gly590Val | missense_variant | 16/28 | ENST00000389054.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.1769G>T | p.Gly590Val | missense_variant | 16/28 | 5 | NM_005219.5 | A2 | |
DIAPH1 | ENST00000518047.5 | c.1742G>T | p.Gly581Val | missense_variant | 15/27 | 5 | P4 | ||
DIAPH1 | ENST00000647433.1 | c.1769G>T | p.Gly590Val | missense_variant | 16/29 | A2 | |||
DIAPH1 | ENST00000647330.1 | c.*996G>T | 3_prime_UTR_variant, NMD_transcript_variant | 15/15 |
Frequencies
GnomAD3 genomes ? AF: 0.00149 AC: 226AN: 151414Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00123 AC: 304AN: 247096Hom.: 1 AF XY: 0.00119 AC XY: 160AN XY: 133990
GnomAD4 exome AF: 0.00148 AC: 2164AN: 1460606Hom.: 3 Cov.: 36 AF XY: 0.00154 AC XY: 1120AN XY: 726458
GnomAD4 genome ? AF: 0.00149 AC: 226AN: 151532Hom.: 0 Cov.: 31 AF XY: 0.00143 AC XY: 106AN XY: 74022
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 05, 2020 | This variant is associated with the following publications: (PMID: 23804846) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 21, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | DIAPH1: BP4, BS1, BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 14, 2017 | p.Gly590Val in exon 16 of DIAPH1: This variant is not expected to have clinical significance because it has been identified in 0.3% (69/25716) of Finnish and 0. 2% (283/125346) of European chromosomes, including 1 homozygous individual, by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs189809247). - |
Autosomal dominant nonsyndromic hearing loss 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
DIAPH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 25, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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 | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at