17-67340886-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002816.5(PSMD12):c.1328C>T(p.Thr443Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,440,572 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_002816.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PSMD12 | NM_002816.5 | c.1328C>T | p.Thr443Met | missense_variant | Exon 11 of 11 | ENST00000356126.8 | NP_002807.1 | |
PSMD12 | NM_174871.4 | c.1268C>T | p.Thr423Met | missense_variant | Exon 10 of 10 | NP_777360.1 | ||
PSMD12 | NM_001316341.2 | c.1151C>T | p.Thr384Met | missense_variant | Exon 13 of 13 | NP_001303270.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSMD12 | ENST00000356126.8 | c.1328C>T | p.Thr443Met | missense_variant | Exon 11 of 11 | 1 | NM_002816.5 | ENSP00000348442.3 | ||
PSMD12 | ENST00000584008.5 | n.*1483C>T | non_coding_transcript_exon_variant | Exon 13 of 13 | 1 | ENSP00000462525.1 | ||||
PSMD12 | ENST00000584008.5 | n.*1483C>T | 3_prime_UTR_variant | Exon 13 of 13 | 1 | ENSP00000462525.1 | ||||
PSMD12 | ENST00000357146.4 | c.1268C>T | p.Thr423Met | missense_variant | Exon 10 of 10 | 2 | ENSP00000349667.4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome AF: 0.0000118 AC: 17AN: 1440572Hom.: 0 Cov.: 30 AF XY: 0.00000837 AC XY: 6AN XY: 716436
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Stankiewicz-Isidor syndrome Uncertain:1
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Stankiewicz-Isidor syndrome (MIM#617516). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from threonine to methionine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated RPN5_C domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited (by trio analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at