rs372148301
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014714.4(IFT140):c.128T>C(p.Val43Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. V43M) has been classified as Uncertain significance.
Frequency
Consequence
NM_014714.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT140 | NM_014714.4 | c.128T>C | p.Val43Ala | missense_variant | 3/31 | ENST00000426508.7 | |
LOC105371046 | NR_135176.1 | n.127+2657A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT140 | ENST00000426508.7 | c.128T>C | p.Val43Ala | missense_variant | 3/31 | 5 | NM_014714.4 | P1 | |
ENST00000563162.1 | n.127+2657A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251414Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135884
GnomAD4 exome AF: 0.000150 AC: 219AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 98AN XY: 727230
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74342
ClinVar
Submissions by phenotype
Saldino-Mainzer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2022 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 43 of the IFT140 protein (p.Val43Ala). This variant is present in population databases (rs372148301, gnomAD 0.01%). This missense change has been observed in individual(s) with IFT140-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 533865). 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 IFT140 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