rs746597198
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_022114.4(PRDM16):c.658G>A(p.Val220Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000695 in 1,439,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. V220L) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.658G>A | p.Val220Met | missense_variant | 5/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.658G>A | p.Val220Met | missense_variant | 5/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.658G>A | p.Val220Met | missense_variant | 5/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000695 AC: 10AN: 1439296Hom.: 0 Cov.: 28 AF XY: 0.0000126 AC XY: 9AN XY: 714886
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Left ventricular noncompaction 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 17, 2019 | This sequence change replaces valine with methionine at codon 220 of the PRDM16 protein (p.Val220Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PRDM16-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at