rs34592408
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000135.4(FANCA):āc.1928C>Gā(p.Pro643Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,551,470 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P643A) has been classified as Benign.
Frequency
Consequence
NM_000135.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.1928C>G | p.Pro643Arg | missense_variant | 22/43 | ENST00000389301.8 | |
FANCA | NM_001286167.3 | c.1928C>G | p.Pro643Arg | missense_variant | 22/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.1928C>G | p.Pro643Arg | missense_variant | 22/43 | 1 | NM_000135.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00544 AC: 827AN: 152126Hom.: 6 Cov.: 32
GnomAD3 exomes AF: 0.00126 AC: 197AN: 156182Hom.: 1 AF XY: 0.000986 AC XY: 81AN XY: 82156
GnomAD4 exome AF: 0.000526 AC: 736AN: 1399226Hom.: 8 Cov.: 31 AF XY: 0.000443 AC XY: 306AN XY: 690114
GnomAD4 genome AF: 0.00544 AC: 828AN: 152244Hom.: 6 Cov.: 32 AF XY: 0.00513 AC XY: 382AN XY: 74458
ClinVar
Submissions by phenotype
not specified Benign:2Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 29, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 09, 2021 | - - |
Fanconi anemia complementation group A Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Fanconi anemia Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at