chr14-45154709-C-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_020937.4(FANCM):āc.1196C>Gā(p.Ser399Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,445,034 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 Pathogenic (ā ). Synonymous variant affecting the same amino acid position (i.e. S399S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_020937.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCM | NM_020937.4 | c.1196C>G | p.Ser399Ter | stop_gained | 7/23 | ENST00000267430.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCM | ENST00000267430.10 | c.1196C>G | p.Ser399Ter | stop_gained | 7/23 | 1 | NM_020937.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000692 AC: 10AN: 1445034Hom.: 0 Cov.: 27 AF XY: 0.00000834 AC XY: 6AN XY: 719266
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 08, 2019 | This sequence change creates a premature translational stop signal (p.Ser399*) in the FANCM gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in FANCM are known to be pathogenic (PMID: 29895858, 30075111). This variant has not been reported in the literature in individuals with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID:Ā¬ā 456250). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at