12-112453210-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_002834.5(PTPN11):āc.348T>Gā(p.His116Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,156 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Consequence
NM_002834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTPN11 | ENST00000351677.7 | c.348T>G | p.His116Gln | missense_variant | Exon 4 of 16 | 1 | NM_002834.5 | ENSP00000340944.3 | ||
PTPN11 | ENST00000635625.1 | c.348T>G | p.His116Gln | missense_variant | Exon 4 of 15 | 5 | ENSP00000489597.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251058Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135746
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459946Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726290
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
The p.H116Q variant (also known as c.348T>G), located in coding exon 4 of the PTPN11 gene, results from a T to G substitution at nucleotide position 348. The histidine at codon 116 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at