1-10461600-G-A
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_004401.3(DFFA):c.886C>T(p.Arg296Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00218 in 1,614,216 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0023 ( 8 hom. )
Consequence
DFFA
NM_004401.3 missense
NM_004401.3 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 4.42
Genes affected
DFFA (HGNC:2772): (DNA fragmentation factor subunit alpha) Apoptosis is a cell death process that removes toxic and/or useless cells during mammalian development. The apoptotic process is accompanied by shrinkage and fragmentation of the cells and nuclei and degradation of the chromosomal DNA into nucleosomal units. DNA fragmentation factor (DFF) is a heterodimeric protein of 40-kD (DFFB) and 45-kD (DFFA) subunits. DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. DFF becomes activated when DFFA is cleaved by caspase-3. The cleaved fragments of DFFA dissociate from DFFB, the active component of DFF. DFFB has been found to trigger both DNA fragmentation and chromatin condensation during apoptosis. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.014656097).
BP6
Variant 1-10461600-G-A is Benign according to our data. Variant chr1-10461600-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 771301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAdExome4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DFFA | NM_004401.3 | c.886C>T | p.Arg296Cys | missense_variant | 6/6 | ENST00000377038.8 | |
DFFA | NM_213566.2 | c.*1434C>T | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DFFA | ENST00000377038.8 | c.886C>T | p.Arg296Cys | missense_variant | 6/6 | 1 | NM_004401.3 | P1 | |
DFFA | ENST00000476658.5 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00126 AC: 192AN: 152208Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00174 AC: 437AN: 251452Hom.: 0 AF XY: 0.00166 AC XY: 226AN XY: 135904
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GnomAD4 exome AF: 0.00228 AC: 3333AN: 1461890Hom.: 8 Cov.: 31 AF XY: 0.00222 AC XY: 1616AN XY: 727246
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GnomAD4 genome AF: 0.00125 AC: 191AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.00107 AC XY: 80AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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gMVP
Splicing
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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