rs757964568
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_181460.4(PAX3):c.1202C>T(p.Ser401Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,613,744 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_181460.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PAX3 | NM_181458.4 | c.1449C>T | p.Ile483Ile | synonymous_variant | 9/9 | ENST00000392070.7 | NP_852123.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PAX3 | ENST00000392070.7 | c.1449C>T | p.Ile483Ile | synonymous_variant | 9/9 | 1 | NM_181458.4 | ENSP00000375922.3 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 151944Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000140 AC: 35AN: 250390Hom.: 0 AF XY: 0.0000812 AC XY: 11AN XY: 135396
GnomAD4 exome AF: 0.000176 AC: 257AN: 1461800Hom.: 2 Cov.: 34 AF XY: 0.000164 AC XY: 119AN XY: 727200
GnomAD4 genome AF: 0.000132 AC: 20AN: 151944Hom.: 0 Cov.: 31 AF XY: 0.0000943 AC XY: 7AN XY: 74206
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 21, 2016 | c.1202C>T (p.Ser401Leu) in exon 8E of PAX3: This variant is not expected to hav e clinical significance. It is located in an alternate transcript (NM_181461.3) in which the variant nucleotide (T) is present in over 10 mammals, despite high conservation at the adjacent nucleotides. This variant is also translated to a silent variant in the major transcript (NM_001127366.2, c.1446C>T, p.Ile482Ile) , and it is in noncoding regions of other alternate transcripts (NM_000438.5, NM _013942.4, NM_181457.3). This variant has been identified in 0.1% (9/8612) of E ast Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org). In summary, this variant is likely benign due to the lack of nucleotide conservation and predicted impact on the gene function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at