rs1555575253
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.401_402insC(p.Val135CysfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,030 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P134P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000135.4 frameshift
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.401_402insC | p.Val135CysfsTer46 | frameshift_variant | 4/43 | ENST00000389301.8 | |
FANCA | NM_001018112.3 | c.401_402insC | p.Val135CysfsTer46 | frameshift_variant | 4/11 | ||
FANCA | NM_001286167.3 | c.401_402insC | p.Val135CysfsTer46 | frameshift_variant | 4/43 | ||
FANCA | NM_001351830.2 | c.401_402insC | p.Val135CysfsTer14 | frameshift_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.401_402insC | p.Val135CysfsTer46 | frameshift_variant | 4/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251278Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727178
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74388
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:2
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 30, 2018 | - - |
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 01, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 558097). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 9371798). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Val135Cysfs*46) 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