rs878854980
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_014425.5(INVS):āc.1379T>Gā(p.Leu460Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_014425.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
INVS | NM_014425.5 | c.1379T>G | p.Leu460Trp | missense_variant | 10/17 | ENST00000262457.7 | NP_055240.2 | |
INVS | NM_001318381.2 | c.1091T>G | p.Leu364Trp | missense_variant | 11/18 | NP_001305310.1 | ||
INVS | NM_001318382.2 | c.401T>G | p.Leu134Trp | missense_variant | 10/17 | NP_001305311.1 | ||
INVS | NR_134606.2 | n.1577T>G | non_coding_transcript_exon_variant | 10/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
INVS | ENST00000262457.7 | c.1379T>G | p.Leu460Trp | missense_variant | 10/17 | 1 | NM_014425.5 | ENSP00000262457.2 | ||
INVS | ENST00000262456.6 | c.1379T>G | p.Leu460Trp | missense_variant | 10/18 | 5 | ENSP00000262456.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 26, 2020 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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 INVS-related conditions. ClinVar contains an entry for this variant (Variation ID: 240909). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with tryptophan at codon 460 of the INVS protein (p.Leu460Trp). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and tryptophan. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at