NM_181458.4:c.944C>A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_181458.4(PAX3):c.944C>A(p.Thr315Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0357 in 1,613,850 control chromosomes in the GnomAD database, including 1,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_181458.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0253 AC: 3855AN: 152124Hom.: 76 Cov.: 32
GnomAD3 exomes AF: 0.0268 AC: 6723AN: 251172Hom.: 121 AF XY: 0.0271 AC XY: 3680AN XY: 135740
GnomAD4 exome AF: 0.0367 AC: 53689AN: 1461608Hom.: 1173 Cov.: 31 AF XY: 0.0365 AC XY: 26518AN XY: 727126
GnomAD4 genome AF: 0.0253 AC: 3854AN: 152242Hom.: 76 Cov.: 32 AF XY: 0.0246 AC XY: 1834AN XY: 74448
ClinVar
Submissions by phenotype
not specified Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Thr314Lys in exon 6 of PAX3: This variant is not expected to have clinical signi ficance because it has been identified in 3.8% (326/8600) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs2234675). -
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not provided Benign:2
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Congenital diaphragmatic hernia Uncertain:1
It is unclear whether these changes, alone or in aggregate, are contributing to the development of CDH in this family. -
Craniofacial-deafness-hand syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Waardenburg syndrome type 1 Benign:1
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Waardenburg syndrome Benign:1
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at