chr16-89740818-G-GT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000135.4(FANCA):c.3813_3814insA(p.His1272ThrfsTer6) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. S1271S) 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.3813_3814insA | p.His1272ThrfsTer6 | frameshift_variant | 38/43 | ENST00000389301.8 | |
ZNF276 | NM_001113525.2 | c.*2573dup | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3813_3814insA | p.His1272ThrfsTer6 | frameshift_variant | 38/43 | 1 | NM_000135.4 | P1 | |
ZNF276 | ENST00000443381.7 | c.*2573dup | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74288
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 20, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 09, 2021 | - - |
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 | Counsyl | Feb 15, 2018 | - - |
Fanconi anemia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | ClinVar contains an entry for this variant (Variation ID: 556740). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with fanconi anemia (PMID: 15643609, 29098742). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His1272Thrfs*6) 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