rs1335130331
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The NM_005219.5(DIAPH1):c.3439-3del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_005219.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DIAPH1 | NM_005219.5 | c.3439-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000389054.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DIAPH1 | ENST00000389054.8 | c.3439-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_005219.5 | A2 | |||
DIAPH1 | ENST00000518047.5 | c.3412-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 | ||||
DIAPH1 | ENST00000647433.1 | c.3439-3del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249476Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135356
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 30, 2018 | The c.3439-3delC variant in DIAPH1 has not been previously reported in individua ls with hearing loss, but has been identified in 0.0008% (1/113216) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 475707). The c.3439-3delC variant is loca ted in the 3' splice region. Computational tools do not predict a splicing impac t, though this information is not predictive enough to rule out pathogenicity. I n summary, the clinical significance of this variant is uncertain. ACMG/AMP Crit eria applied: PM2, BP4. - |
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 | Sep 12, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at