4-185504544-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014476.6(PDLIM3):c.836C>T(p.Thr279Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,614,000 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. T279K) has been classified as Uncertain significance.
Frequency
Consequence
NM_014476.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM3 | NM_014476.6 | c.836C>T | p.Thr279Met | missense_variant | 7/8 | ENST00000284767.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM3 | ENST00000284767.12 | c.836C>T | p.Thr279Met | missense_variant | 7/8 | 5 | NM_014476.6 | A1 | |
ENST00000671042.1 | n.518-1957G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251398Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135888
GnomAD4 exome AF: 0.0000472 AC: 69AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 727236
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74302
ClinVar
Submissions by phenotype
Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 279 of the PDLIM3 protein (p.Thr279Met). This variant is present in population databases (rs150070443, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with PDLIM3-related conditions. ClinVar contains an entry for this variant (Variation ID: 240917). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDLIM3 protein function. 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