chr9-95099543-C-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000136.3(FANCC):c.*2164G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000908 in 230,274 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00038 ( 0 hom. )
Consequence
FANCC
NM_000136.3 3_prime_UTR
NM_000136.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.188
Genes affected
FANCC (HGNC:3584): (FA complementation group C) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group C. [provided by RefSeq, Jul 2008]
AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCC | NM_000136.3 | c.*2164G>T | 3_prime_UTR_variant | 15/15 | ENST00000289081.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCC | ENST00000289081.8 | c.*2164G>T | 3_prime_UTR_variant | 15/15 | 1 | NM_000136.3 | P1 | ||
FANCC | ENST00000375305.6 | c.*2164G>T | 3_prime_UTR_variant | 15/15 | 1 | P1 | |||
FANCC | ENST00000696260.1 | n.4656G>T | non_coding_transcript_exon_variant | 3/3 | |||||
AOPEP | ENST00000710812.1 | n.410+18763C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00118 AC: 179AN: 151666Hom.: 1 Cov.: 31
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GnomAD4 exome AF: 0.000382 AC: 30AN: 78490Hom.: 0 Cov.: 0 AF XY: 0.000332 AC XY: 12AN XY: 36134
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GnomAD4 genome AF: 0.00118 AC: 179AN: 151784Hom.: 1 Cov.: 31 AF XY: 0.00169 AC XY: 125AN XY: 74154
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Fanconi anemia complementation group C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at