rs551306400
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000135.4(FANCA):c.3937C>T(p.Leu1313Phe) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,551,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000135.4 missense, splice_region
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.3937C>T | p.Leu1313Phe | missense_variant, splice_region_variant | 40/43 | ENST00000389301.8 | NP_000126.2 | |
ZNF276 | NM_001113525.2 | c.*1305G>A | 3_prime_UTR_variant | 11/11 | ENST00000443381.7 | NP_001106997.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FANCA | ENST00000389301.8 | c.3937C>T | p.Leu1313Phe | missense_variant, splice_region_variant | 40/43 | 1 | NM_000135.4 | ENSP00000373952 | P1 | |
ZNF276 | ENST00000443381.7 | c.*1305G>A | 3_prime_UTR_variant | 11/11 | 1 | NM_001113525.2 | ENSP00000415836 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000644 AC: 1AN: 155290Hom.: 0 AF XY: 0.0000122 AC XY: 1AN XY: 81976
GnomAD4 exome AF: 0.00000643 AC: 9AN: 1398894Hom.: 0 Cov.: 33 AF XY: 0.00000580 AC XY: 4AN XY: 689980
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74462
ClinVar
Submissions by phenotype
Fanconi anemia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 08, 2024 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1313 of the FANCA protein (p.Leu1313Phe). This variant is present in population databases (rs551306400, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 408178). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. | Feb 21, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2022 | The c.3937C>T (p.L1313F) alteration is located in exon 40 (coding exon 40) of the FANCA gene. This alteration results from a C to T substitution at nucleotide position 3937, causing the leucine (L) at amino acid position 1313 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2022 | Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at