1-3417991-C-T
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_022114.4(PRDM16):c.2855C>T(p.Thr952Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000993 in 1,610,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T952K) has been classified as Uncertain significance.
Frequency
Consequence
NM_022114.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.2855C>T | p.Thr952Met | missense_variant | 11/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.2855C>T | p.Thr952Met | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.2855C>T | p.Thr952Met | missense_variant | 11/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000246 AC: 6AN: 244080Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133296
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1458708Hom.: 0 Cov.: 35 AF XY: 0.00000965 AC XY: 7AN XY: 725374
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
Wolff-Parkinson-White pattern Uncertain:1
Uncertain significance, no assertion criteria provided | research | Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine | Jul 14, 2017 | This variant was identified in an individual with Wolff-Parkinson-White syndrome - |
Left ventricular noncompaction 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 487592). This missense change has been observed in individual(s) with Wolf-Parkinson-White syndrome (PMID: 32233023). This variant is present in population databases (rs749180764, ExAC 0.01%). This sequence change replaces threonine with methionine at codon 952 of the PRDM16 protein (p.Thr952Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at