chr20-43596472-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016004.5(IFT52):c.157G>A(p.Val53Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000765 in 1,607,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. V53V) has been classified as Benign.
Frequency
Consequence
NM_016004.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT52 | NM_016004.5 | c.157G>A | p.Val53Met | missense_variant | 3/14 | ENST00000373030.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT52 | ENST00000373030.8 | c.157G>A | p.Val53Met | missense_variant | 3/14 | 1 | NM_016004.5 | P1 | |
IFT52 | ENST00000373039.4 | c.157G>A | p.Val53Met | missense_variant | 3/14 | 5 | P1 | ||
IFT52 | ENST00000486243.1 | n.134G>A | non_coding_transcript_exon_variant | 2/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000105 AC: 26AN: 248554Hom.: 0 AF XY: 0.0000670 AC XY: 9AN XY: 134364
GnomAD4 exome AF: 0.0000412 AC: 60AN: 1455256Hom.: 0 Cov.: 26 AF XY: 0.0000428 AC XY: 31AN XY: 724118
GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152298Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74456
ClinVar
Submissions by phenotype
Short-rib thoracic dysplasia 16 with or without polydactyly Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein | Jul 06, 2021 | ACMG classification criteria: PM2 moderate, BP4 supporting - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 53 of the IFT52 protein (p.Val53Met). This variant is present in population databases (rs137979762, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with IFT52-related conditions. ClinVar contains an entry for this variant (Variation ID: 1427662). 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) performed at Invitae indicates that this missense variant is not expected to disrupt IFT52 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