2-7024394-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014746.6(RNF144A):c.535G>A(p.Asp179Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000909 in 1,609,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00092 ( 1 hom. )
Consequence
RNF144A
NM_014746.6 missense
NM_014746.6 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.83
Genes affected
RNF144A (HGNC:20457): (ring finger protein 144A) This gene encodes a member of a family of RING finger domain-containing E3 ubiquitin ligases that also includes parkin and parc. The expression of this gene is induced by DNA damage. The encoded protein interacts with the cytoplasmic DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and promotes its degradation through ubiquitination. The orthologous mouse protein has been shown to interact with a ubiquitin-conjugating enzyme involved in embryonic development. [provided by RefSeq, Mar 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011024326).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF144A | NM_014746.6 | c.535G>A | p.Asp179Asn | missense_variant | 7/9 | ENST00000320892.11 | NP_055561.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF144A | ENST00000320892.11 | c.535G>A | p.Asp179Asn | missense_variant | 7/9 | 1 | NM_014746.6 | ENSP00000321330 | P1 | |
RNF144A | ENST00000432850.1 | c.523G>A | p.Asp175Asn | missense_variant | 5/7 | 3 | ENSP00000411616 | |||
RNF144A | ENST00000467276.5 | n.656G>A | non_coding_transcript_exon_variant | 4/6 | 3 | |||||
RNF144A | ENST00000480970.1 | n.581G>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000795 AC: 121AN: 152222Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000653 AC: 164AN: 251296Hom.: 0 AF XY: 0.000692 AC XY: 94AN XY: 135816
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GnomAD4 exome AF: 0.000921 AC: 1342AN: 1457056Hom.: 1 Cov.: 31 AF XY: 0.000880 AC XY: 637AN XY: 723636
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GnomAD4 genome AF: 0.000795 AC: 121AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000699 AC XY: 52AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 03, 2021 | The c.535G>A (p.D179N) alteration is located in exon 7 (coding exon 5) of the RNF144A gene. This alteration results from a G to A substitution at nucleotide position 535, causing the aspartic acid (D) at amino acid position 179 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
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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