rs751847293
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BP6BS2_Supporting
The NM_005219.5(DIAPH1):c.2009C>T(p.Pro670Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000983 in 1,526,198 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 Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.2009C>T | p.Pro670Leu | missense_variant | Exon 16 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
DIAPH1 | ENST00000518047.5 | c.1982C>T | p.Pro661Leu | missense_variant | Exon 15 of 27 | 5 | ENSP00000428268.2 | |||
DIAPH1 | ENST00000647433.1 | c.2009C>T | p.Pro670Leu | missense_variant | Exon 16 of 29 | ENSP00000494675.1 |
Frequencies
GnomAD3 genomes AF: 0.0000133 AC: 2AN: 150508Hom.: 0 Cov.: 25
GnomAD3 exomes AF: 0.0000359 AC: 5AN: 139368Hom.: 0 AF XY: 0.0000140 AC XY: 1AN XY: 71196
GnomAD4 exome AF: 0.00000945 AC: 13AN: 1375690Hom.: 0 Cov.: 36 AF XY: 0.00000445 AC XY: 3AN XY: 674018
GnomAD4 genome AF: 0.0000133 AC: 2AN: 150508Hom.: 0 Cov.: 25 AF XY: 0.0000136 AC XY: 1AN XY: 73392
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 proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 670 of the DIAPH1 protein (p.Pro670Leu). This variant is present in population databases (rs751847293, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of DIAPH1-related conditions (PMID: 30896630). This variant is also known as c.1982C>T (p.Pro661Leu). ClinVar contains an entry for this variant (Variation ID: 475700). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at