11-22257708-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BS2_Supporting
The NM_213599.3(ANO5):c.1361C>T(p.Thr454Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000484 in 1,612,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T454K) has been classified as Uncertain significance.
Frequency
Consequence
NM_213599.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO5 | NM_213599.3 | c.1361C>T | p.Thr454Met | missense_variant | 14/22 | ENST00000324559.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO5 | ENST00000324559.9 | c.1361C>T | p.Thr454Met | missense_variant | 14/22 | 1 | NM_213599.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152066Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251160Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135748
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1460270Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34AN XY: 726552
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74416
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 30, 2020 | - - |
Gnathodiaphyseal dysplasia;C1969785:Autosomal recessive limb-girdle muscular dystrophy type 2L Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at