16-89746857-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):āc.3382C>Gā(p.Gln1128Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000448 in 1,562,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_000135.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.3382C>G | p.Gln1128Glu | missense_variant | 34/43 | ENST00000389301.8 | NP_000126.2 | |
FANCA | NM_001286167.3 | c.3382C>G | p.Gln1128Glu | missense_variant | 34/43 | NP_001273096.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3382C>G | p.Gln1128Glu | missense_variant | 34/43 | 1 | NM_000135.4 | ENSP00000373952 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000355 AC: 5AN: 1410264Hom.: 0 Cov.: 32 AF XY: 0.00000431 AC XY: 3AN XY: 696772
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | curation | Leiden Open Variation Database | Feb 28, 2020 | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Nov 08, 2021 | NM_000135.2(FANCA):c.3382C>G(Q1128E) is a missense variant classified as a variant of uncertain significance in the context of Fanconi anemia complementation group A. Q1128E has been observed in cases with relevant disease (PMID: 9371798). Functional assessments of this variant are available in the literature (PMID: 30057198, 12444097, 16946016). Q1128E has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000135.2(FANCA):c.3382C>G(Q1128E) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. - |
Fanconi anemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 03, 2022 | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1128 of the FANCA protein (p.Gln1128Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Fanconi anemia (PMID: 9371798). ClinVar contains an entry for this variant (Variation ID: 551847). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FANCA protein function. Experimental studies have shown that this missense change affects FANCA function (PMID: 16946016, 30057198). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 20, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at