8-28503150-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_017412.4(FZD3):āc.137T>Cā(p.Met46Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,320 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M46L) has been classified as Uncertain significance.
Frequency
Consequence
NM_017412.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FZD3 | NM_017412.4 | c.137T>C | p.Met46Thr | missense_variant | 3/8 | ENST00000240093.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FZD3 | ENST00000240093.8 | c.137T>C | p.Met46Thr | missense_variant | 3/8 | 1 | NM_017412.4 | P1 | |
FZD3 | ENST00000537916.2 | c.137T>C | p.Met46Thr | missense_variant | 2/7 | 2 | P1 | ||
FZD3 | ENST00000523546.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251356Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135850
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461320Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 727022
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 03, 2022 | The c.137T>C (p.M46T) alteration is located in exon 3 (coding exon 1) of the FZD3 gene. This alteration results from a T to C substitution at nucleotide position 137, causing the methionine (M) at amino acid position 46 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