rs864622188
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):βc.416_417delβ(p.Val139GlyfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. V139V) 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.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | ENST00000389301.8 | |
FANCA | NM_001018112.3 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/11 | ||
FANCA | NM_001286167.3 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | ||
FANCA | NM_001351830.2 | c.416_417del | p.Val139GlyfsTer9 | frameshift_variant | 4/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461798Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Fanconi anemia Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 22, 2023 | This sequence change creates a premature translational stop signal (p.Val139Glyfs*41) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Fanconi anemia (PMID: 15643609). ClinVar contains an entry for this variant (Variation ID: 219633). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 08, 2021 | - - |
Fanconi anemia complementation group A Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 24, 2023 | - - |
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Sue Richards. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at