22-29049469-G-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_001206998.2(ZNRF3):c.1288G>A(p.Ala430Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,604,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001206998.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNRF3 | NM_001206998.2 | c.1288G>A | p.Ala430Thr | missense_variant | 8/9 | ENST00000544604.7 | |
ZNRF3 | NM_032173.4 | c.988G>A | p.Ala330Thr | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNRF3 | ENST00000544604.7 | c.1288G>A | p.Ala430Thr | missense_variant | 8/9 | 1 | NM_001206998.2 | A2 | |
ZNRF3 | ENST00000406323.3 | c.988G>A | p.Ala330Thr | missense_variant | 7/8 | 1 | P2 | ||
ZNRF3 | ENST00000402174.5 | c.988G>A | p.Ala330Thr | missense_variant | 8/9 | 2 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151898Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1452478Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 723010
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151898Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74172
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2022 | The c.1288G>A (p.A430T) alteration is located in exon 8 (coding exon 8) of the ZNRF3 gene. This alteration results from a G to A substitution at nucleotide position 1288, causing the alanine (A) at amino acid position 430 to be replaced by a threonine (T). 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