9-130681605-TCGCCGCCGCCGCCGCCGCCGCCGC-TCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGCCGC
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP3
The NM_021619.3(PRDM12):c.1062_1076dupCGCCGCCGCCGCCGC(p.Ala355_Ala359dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00015 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PRDM12
NM_021619.3 disruptive_inframe_insertion
NM_021619.3 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0910
Genes affected
PRDM12 (HGNC:13997): (PR/SET domain 12) This gene encodes a transcriptional regulator of sensory neuronal specification that plays a critical role in pain perception. The encoded protein contains an N-terminal PRDI-BF1 and RIZ homology (PR) domain, a SET domain, and three C-terminal C2H2 zinc finger DNA-binding domains. Naturally occurring mutations in this gene are associated with congenital insensitivity to pain (CIP), and hereditary sensory and autonomic neuropathies (HSAN's) affecting peripheral sensory and autonomic neurons. Deregulation of this gene is associated with solid cancers and hematological malignancies including chronic myeloid leukaemia. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_021619.3
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM12 | ENST00000253008.3 | c.1062_1076dupCGCCGCCGCCGCCGC | p.Ala355_Ala359dup | disruptive_inframe_insertion | 5/5 | 1 | NM_021619.3 | ENSP00000253008.2 | ||
PRDM12 | ENST00000676323.1 | c.906+156_906+170dupCGCCGCCGCCGCCGC | intron_variant | ENSP00000502471.1 |
Frequencies
GnomAD3 genomes AF: 0.000416 AC: 59AN: 141876Hom.: 0 Cov.: 0
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000155 AC: 126AN: 813284Hom.: 0 Cov.: 6 AF XY: 0.000162 AC XY: 61AN XY: 377226
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GnomAD4 genome AF: 0.000416 AC: 59AN: 141916Hom.: 0 Cov.: 0 AF XY: 0.000393 AC XY: 27AN XY: 68754
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Congenital insensitivity to pain-hypohidrosis syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 24, 2020 | 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. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with PRDM12-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant, c.1062_1076dup, results in the insertion of 5 amino acid(s) to the PRDM12 protein (p.Ala355_Ala359dup), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at