chr22-29048440-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 6P and 4B. PM1PM5PP3_ModerateBS2
The NM_001206998.2(ZNRF3):c.964C>T(p.Pro322Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,614,044 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. P322R) has been classified as Pathogenic.
Frequency
Consequence
NM_001206998.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNRF3 | NM_001206998.2 | c.964C>T | p.Pro322Ser | missense_variant | 7/9 | ENST00000544604.7 | |
ZNRF3 | NM_032173.4 | c.664C>T | p.Pro222Ser | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNRF3 | ENST00000544604.7 | c.964C>T | p.Pro322Ser | missense_variant | 7/9 | 1 | NM_001206998.2 | A2 | |
ZNRF3 | ENST00000406323.3 | c.664C>T | p.Pro222Ser | missense_variant | 6/8 | 1 | P2 | ||
ZNRF3 | ENST00000402174.5 | c.664C>T | p.Pro222Ser | missense_variant | 7/9 | 2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249514Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135374
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727242
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2021 | The c.964C>T (p.P322S) alteration is located in exon 7 (coding exon 7) of the ZNRF3 gene. This alteration results from a C to T substitution at nucleotide position 964, causing the proline (P) at amino acid position 322 to be replaced by a serine (S). 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