rs149775657
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):c.4015C>T(p.Leu1339Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000595 in 1,614,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1339P) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
FANCA | NM_000135.4 | c.4015C>T | p.Leu1339Phe | missense_variant | 41/43 | ENST00000389301.8 | |
ZNF276 | NM_001113525.2 | c.*1039G>A | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.4015C>T | p.Leu1339Phe | missense_variant | 41/43 | 1 | NM_000135.4 | P1 | |
ZNF276 | ENST00000443381.7 | c.*1039G>A | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251296Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135872
GnomAD4 exome AF: 0.0000506 AC: 74AN: 1461776Hom.: 0 Cov.: 35 AF XY: 0.0000440 AC XY: 32AN XY: 727184
GnomAD4 genome AF: 0.000144 AC: 22AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74498
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 26, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 31, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Apr 18, 2017 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jan 12, 2023 | The frequency of this variant in the general population, 0.00028 (7/24954 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported only in a healthy individual (PMID: 24728327 (2014)) and as a somatic variant in an individual with prostate cancer (PMID: 31698007 (2019)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 13, 2022 | - - |
Fanconi anemia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jan 26, 2022 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at