NM_005219.5:c.3175C>G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BS1BS2_Supporting
The NM_005219.5(DIAPH1):āc.3175C>Gā(p.Leu1059Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,469,974 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).
Frequency
Consequence
NM_005219.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.3175C>G | p.Leu1059Val | missense_variant | Exon 24 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.3148C>G | p.Leu1050Val | missense_variant | Exon 23 of 27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000647433.1 | c.3175C>G | p.Leu1059Val | missense_variant | Exon 24 of 29 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.0000434 AC: 6AN: 138292Hom.: 0 Cov.: 28
GnomAD3 exomes AF: 0.000104 AC: 25AN: 240020Hom.: 0 AF XY: 0.0000847 AC XY: 11AN XY: 129868
GnomAD4 exome AF: 0.0000548 AC: 73AN: 1331682Hom.: 0 Cov.: 38 AF XY: 0.0000513 AC XY: 34AN XY: 663140
GnomAD4 genome AF: 0.0000434 AC: 6AN: 138292Hom.: 0 Cov.: 28 AF XY: 0.0000151 AC XY: 1AN XY: 66036
ClinVar
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Uncertain:1
This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1059 of the DIAPH1 protein (p.Leu1059Val). This variant is present in population databases (rs200394036, gnomAD 0.2%). 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: 578663). 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. -
not specified Benign:1
The p.Leu1059Val variant in DIAPH1 is classified as benign because it has been identified in 0.147% (28/19048) of East Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). ACMG/AMP Criteria applied: BA1. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at