chr9-36840610-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_016734.3(PAX5):c.1126G>A(p.Ala376Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000196 in 1,578,774 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 (★★).
Frequency
Consequence
NM_016734.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000854 AC: 16AN: 187302Hom.: 0 AF XY: 0.0000800 AC XY: 8AN XY: 99958
GnomAD4 exome AF: 0.000210 AC: 299AN: 1426718Hom.: 0 Cov.: 30 AF XY: 0.000204 AC XY: 144AN XY: 706016
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74270
ClinVar
Submissions by phenotype
not specified Uncertain:1
DNA sequence analysis of the PAX5 gene demonstrated a sequence change, c.1126G>A, in exon 10 that results in an amino acid change, p.Ala376Thr. This sequence change does not appear to have been previously described in individuals with PAX5-related disorders. This sequence change has been described in the gnomAD database with a low frequency of 0.015% in the African/African American subpopulation (dbSNP rs528158465). The p.Ala376Thr change affects a highly conserved amino acid residue located in a domain of the PAX5 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Ala376Thr substitution. Due to insufficient evidence and the lack of functional studies, the clinical significance of the p.Ala376Thr change remains unknown at this time. -
not provided Uncertain:1
In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at