rs144391508
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002834.5(PTPN11):c.854-30T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 1,561,580 control chromosomes in the GnomAD database, including 484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..
Frequency
Consequence
NM_002834.5 intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00929 AC: 1414AN: 152184Hom.: 67 Cov.: 32
GnomAD3 exomes AF: 0.0180 AC: 4523AN: 251170Hom.: 325 AF XY: 0.0136 AC XY: 1844AN XY: 135746
GnomAD4 exome AF: 0.00426 AC: 6007AN: 1409278Hom.: 414 Cov.: 27 AF XY: 0.00357 AC XY: 2512AN XY: 704228
GnomAD4 genome AF: 0.00936 AC: 1425AN: 152302Hom.: 70 Cov.: 32 AF XY: 0.0109 AC XY: 809AN XY: 74466
ClinVar
Submissions by phenotype
not specified Benign:3
- -
- -
Variant summary: The PTPN11 c.854-30T>C variant involves the alteration of a non-conserved intronic nucleotide and 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4526/276876 control chromosomes (320 homozygotes) (gnomAD), predominantly observed in the Latino subpopulation at a frequency of 0.126476 (4349/34386). This frequency is about 2000 times the estimated maximal expected allele frequency of a pathogenic PTPN11 variant (0.0000625), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign. -
not provided Benign:2
- -
- -
Noonan syndrome Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at