20-25274682-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_002862.4(PYGB):c.619G>A(p.Val207Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000157 in 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V207L) has been classified as Uncertain significance.
Frequency
Consequence
NM_002862.4 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 |
---|---|---|---|---|---|---|---|
PYGB | NM_002862.4 | c.619G>A | p.Val207Met | missense_variant | 5/20 | ENST00000216962.9 | |
PYGB | XM_047440342.1 | c.619G>A | p.Val207Met | missense_variant | 5/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYGB | ENST00000216962.9 | c.619G>A | p.Val207Met | missense_variant | 5/20 | 1 | NM_002862.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250714Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135502
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461384Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727018
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2022 | The c.619G>A (p.V207M) alteration is located in exon 5 (coding exon 5) of the PYGB gene. This alteration results from a G to A substitution at nucleotide position 619, causing the valine (V) at amino acid position 207 to be replaced by a methionine (M). 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