16-74624048-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_018124.4(RFWD3):c.2205G>A(p.Ser735=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,611,972 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
RFWD3
NM_018124.4 synonymous
NM_018124.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.36
Genes affected
RFWD3 (HGNC:25539): (ring finger and WD repeat domain 3) Enables MDM2/MDM4 family protein binding activity; p53 binding activity; and ubiquitin protein ligase activity. Involved in several processes, including DNA metabolic process; regulation of cell cycle phase transition; and response to ionizing radiation. Located in nucleoplasm and site of DNA damage. Colocalizes with site of double-strand break. Implicated in Fanconi anemia. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 16-74624048-C-T is Benign according to our data. Variant chr16-74624048-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1185033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.36 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFWD3 | NM_018124.4 | c.2205G>A | p.Ser735= | synonymous_variant | 13/13 | ENST00000361070.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFWD3 | ENST00000361070.9 | c.2205G>A | p.Ser735= | synonymous_variant | 13/13 | 1 | NM_018124.4 | P1 | |
RFWD3 | ENST00000571750.5 | c.2205G>A | p.Ser735= | synonymous_variant | 14/14 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152006Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000648 AC: 16AN: 246904Hom.: 1 AF XY: 0.0000374 AC XY: 5AN XY: 133796
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1459848Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17AN XY: 726192
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fanconi anemia, complementation group W Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Johns Hopkins Genomics, Johns Hopkins University | Jun 23, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at