rs142960268
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001025356.3(ANO6):c.1274G>A(p.Arg425Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,614,100 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001025356.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANO6 | NM_001025356.3 | c.1274G>A | p.Arg425Gln | missense_variant | 11/20 | ENST00000320560.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANO6 | ENST00000320560.13 | c.1274G>A | p.Arg425Gln | missense_variant | 11/20 | 1 | NM_001025356.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00166 AC: 253AN: 152170Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00131 AC: 330AN: 251450Hom.: 0 AF XY: 0.00138 AC XY: 187AN XY: 135894
GnomAD4 exome AF: 0.00260 AC: 3805AN: 1461812Hom.: 6 Cov.: 31 AF XY: 0.00248 AC XY: 1800AN XY: 727208
GnomAD4 genome ? AF: 0.00166 AC: 253AN: 152288Hom.: 1 Cov.: 32 AF XY: 0.00156 AC XY: 116AN XY: 74468
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 04, 2023 | Variant summary: ANO6 c.1274G>A (p.Arg425Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0013 in 282850 control chromosomes in the gnomAD database, including 1 homozygotes. However, this gnomad data is not considered conclusive as Scott Syndrome may be a clinically silent disease. To our knowledge, no occurrence of c.1274G>A in individuals affected with Scott Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as VUS. - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at