rs947863770
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_022114.4(PRDM16):c.3281A>G(p.Lys1094Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000992 in 1,612,290 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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. K1094E) 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.3281A>G | p.Lys1094Arg | missense_variant | 14/17 | ENST00000270722.10 | |
PRDM16 | NM_199454.3 | c.3281A>G | p.Lys1094Arg | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.3281A>G | p.Lys1094Arg | missense_variant | 14/17 | 1 | NM_022114.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248912Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135094
GnomAD4 exome AF: 0.00000959 AC: 14AN: 1460166Hom.: 1 Cov.: 32 AF XY: 0.00000551 AC XY: 4AN XY: 726128
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74302
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Left ventricular noncompaction 8 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1094 of the PRDM16 protein (p.Lys1094Arg). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with dilated cardiomyopathy or hypertrophic cardiomyopathy (PMID: 30847666). ClinVar contains an entry for this variant (Variation ID: 541383). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at