chr9-86282397-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030940.4(ISCA1):c.62C>T(p.Thr21Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000193 in 1,552,506 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. T21T) has been classified as Likely benign.
Frequency
Consequence
NM_030940.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ISCA1 | NM_030940.4 | c.62C>T | p.Thr21Ile | missense_variant | 1/4 | ENST00000375991.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ISCA1 | ENST00000375991.9 | c.62C>T | p.Thr21Ile | missense_variant | 1/4 | 1 | NM_030940.4 | P1 | |
ISCA1 | ENST00000326094.4 | c.62C>T | p.Thr21Ile | missense_variant | 1/4 | 3 | |||
ISCA1 | ENST00000637705.1 | c.18+505C>T | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 34
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1400268Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1AN XY: 690812
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152238Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 11, 2022 | 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 tolerated. This variant has not been reported in the literature in individuals affected with ISCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 21 of the ISCA1 protein (p.Thr21Ile). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at