chr4-153712556-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_173662.4(RNF175):c.785G>A(p.Arg262Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,612,418 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 0 hom. )
Consequence
RNF175
NM_173662.4 missense
NM_173662.4 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 2.94
Genes affected
RNF175 (HGNC:27735): (ring finger protein 175) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in ubiquitin-dependent ERAD pathway. Predicted to be integral component of membrane. Predicted to be active in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33250988).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF175 | NM_173662.4 | c.785G>A | p.Arg262Gln | missense_variant | 8/9 | ENST00000347063.9 | NP_775933.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF175 | ENST00000347063.9 | c.785G>A | p.Arg262Gln | missense_variant | 8/9 | 1 | NM_173662.4 | ENSP00000340979 | P1 | |
RNF175 | ENST00000513656.5 | c.*532G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/7 | 3 | ENSP00000421761 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152154Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000605 AC: 15AN: 247866Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134452
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GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460146Hom.: 0 Cov.: 29 AF XY: 0.0000234 AC XY: 17AN XY: 726374
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GnomAD4 genome AF: 0.000184 AC: 28AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74470
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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.785G>A (p.R262Q) alteration is located in exon 8 (coding exon 8) of the RNF175 gene. This alteration results from a G to A substitution at nucleotide position 785, causing the arginine (R) at amino acid position 262 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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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