16-89810937-CCA-C
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000389301.8(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
ENST00000389301.8 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | ENST00000389301.8 | NP_000126.2 | |
FANCA | NM_001018112.3 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/11 | NP_001018122.1 | ||
FANCA | NM_001286167.3 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | NP_001273096.1 | ||
FANCA | NM_001351830.2 | c.416_417del | p.Val139GlyfsTer9 | frameshift_variant | 4/10 | NP_001338759.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.416_417del | p.Val139GlyfsTer41 | frameshift_variant | 4/43 | 1 | NM_000135.4 | ENSP00000373952 | 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, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 08, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | 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. - |
Fanconi anemia complementation group A Pathogenic:2
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. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at