chr4-105940159-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001033047.3(NPNT):c.590G>A(p.Cys197Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001033047.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPNT | NM_001033047.3 | c.590G>A | p.Cys197Tyr | missense_variant | 6/12 | ENST00000379987.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPNT | ENST00000379987.7 | c.590G>A | p.Cys197Tyr | missense_variant | 6/12 | 1 | NM_001033047.3 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251006Hom.: 0 AF XY: 0.0000590 AC XY: 8AN XY: 135622
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460830Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726766
GnomAD4 genome AF: 0.000269 AC: 41AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.000309 AC XY: 23AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2022 | The c.680G>A (p.C227Y) alteration is located in exon 7 (coding exon 7) of the NPNT gene. This alteration results from a G to A substitution at nucleotide position 680, causing the cysteine (C) at amino acid position 227 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at