rs1184639006
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.718C>T(p.Gln240Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 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 (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000135.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.718C>T | p.Gln240Ter | stop_gained | 8/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.718C>T | p.Gln240Ter | stop_gained | 8/43 | ||
FANCA | NM_001018112.3 | c.718C>T | p.Gln240Ter | stop_gained | 8/11 | ||
FANCA | NM_001351830.2 | c.622C>T | p.Gln208Ter | stop_gained | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.718C>T | p.Gln240Ter | stop_gained | 8/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461644Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727124
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 03, 2017 | - - |
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Daniela Pilonetto, Johan de Winter. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 09, 2023 | - - |
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 551354). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 21273304). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln240*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at