rs781577050
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS2
The NM_005219.5(DIAPH1):c.3313C>T(p.Arg1105Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,112 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1105Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_005219.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIAPH1 | NM_005219.5 | c.3313C>T | p.Arg1105Trp | missense_variant | 25/28 | ENST00000389054.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.3313C>T | p.Arg1105Trp | missense_variant | 25/28 | 5 | NM_005219.5 | A2 | |
DIAPH1 | ENST00000518047.5 | c.3286C>T | p.Arg1096Trp | missense_variant | 24/27 | 5 | P4 | ||
DIAPH1 | ENST00000647433.1 | c.3313C>T | p.Arg1105Trp | missense_variant | 25/29 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152118Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000642 AC: 16AN: 249166Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135204
GnomAD4 exome AF: 0.0000664 AC: 97AN: 1461876Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 49AN XY: 727242
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74454
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2017 | - - |
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1105 of the DIAPH1 protein (p.Arg1105Trp). This variant is present in population databases (rs781577050, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DIAPH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 444663). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Beta-D-mannosidosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center | Apr 12, 2021 | PM2_Moderate, BS2_Strong, BP4_Supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at