rs146975341
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):āc.3848A>Gā(p.Lys1283Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict 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. K1283N) 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.3848A>G | p.Lys1283Arg | missense_variant | 39/43 | ENST00000389301.8 | |
ZNF276 | NM_001113525.2 | c.*1834T>C | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3848A>G | p.Lys1283Arg | missense_variant | 39/43 | 1 | NM_000135.4 | P1 | |
ZNF276 | ENST00000443381.7 | c.*1834T>C | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | P2 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000716 AC: 18AN: 251494Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135922
GnomAD4 exome AF: 0.000215 AC: 314AN: 1461852Hom.: 0 Cov.: 33 AF XY: 0.000198 AC XY: 144AN XY: 727230
GnomAD4 genome AF: 0.000171 AC: 26AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74356
ClinVar
Submissions by phenotype
Fanconi anemia complementation group A Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Feb 17, 2022 | The FANCA c.3848A>G (p.Lys1283Arg) missense change has a maximum subpopulation frequency of 0.017% in gnomAD v2.1.1 ( https://gnomad.broadinstitute.org/variant/16-89806488-T-C ). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Fanconi anemia Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | St. Jude Molecular Pathology, St. Jude Children's Research Hospital | Jul 29, 2021 | The FANCA c.3848A>G (p.Lys1283Arg) missense change has a maximum subpopulation frequency of 0.017% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/16-89806488-T-C). Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.3848A>G (p.K1283R) alteration is located in exon 39 (coding exon 39) of the FANCA gene. This alteration results from a A to G substitution at nucleotide position 3848, causing the lysine (K) at amino acid position 1283 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at