rs773159223
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.154C>T(p.Arg52Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,742 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
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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.154C>T | p.Arg52Ter | stop_gained | 2/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.154C>T | p.Arg52Ter | stop_gained | 2/43 | ||
FANCA | NM_001018112.3 | c.154C>T | p.Arg52Ter | stop_gained | 2/11 | ||
FANCA | NM_001351830.2 | c.154C>T | p.Arg52Ter | stop_gained | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.154C>T | p.Arg52Ter | stop_gained | 2/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152234Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251492Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135920
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461742Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727174
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152234Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74372
ClinVar
Submissions by phenotype
Fanconi anemia Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change creates a premature translational stop signal (p.Arg52*) 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). This variant is present in population databases (rs773159223, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 10094191, 28973083). ClinVar contains an entry for this variant (Variation ID: 371668). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 04, 2021 | - - |
Pathogenic, no assertion criteria provided | research | Department of Traditional Chinese Medicine, Fujian Provincial Hospital | - | FANCA (P.R52*) is a nonsense mutation that is predicted to produce truncated expressed proteins with loss of their normal function; it has been reported in the literature [PMID:28973083,10094191] that this variant has been detected in patients with Fanconi anaemia; it is not included in the ESP6500, 1000genomics databases, and is available in the dbSNP and Goldfields reference population databases (rs773159223, 000002), and ClinVar database as Pathogenic. in summary, this variant is classified as pathogenic according to the ACMG guidelines. - |
Fanconi anemia complementation group A Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 10, 2016 | - - |
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at