rs121912987
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PM5PP2PP3_ModeratePP5
The NM_014208.3(DSPP):c.52G>T(p.Val18Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V18A) has been classified as Uncertain significance.
Frequency
Consequence
NM_014208.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSPP | NM_014208.3 | c.52G>T | p.Val18Phe | missense_variant, splice_region_variant | 3/5 | ENST00000651931.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSPP | ENST00000651931.1 | c.52G>T | p.Val18Phe | missense_variant, splice_region_variant | 3/5 | NM_014208.3 | P1 | ||
ENST00000506480.5 | n.323-43572C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461492Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727046
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Deafness, autosomal dominant nonsyndromic sensorineural 39, with dentinogenesis imperfecta 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2012 | - - |
Dentinogenesis imperfecta type 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2012 | - - |
Dentinogenesis imperfecta type 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at