4-153720281-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173662.4(RNF175):āc.533A>Gā(p.Asp178Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.000021 ( 0 hom. )
Consequence
RNF175
NM_173662.4 missense
NM_173662.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 5.56
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNF175 | NM_173662.4 | c.533A>G | p.Asp178Gly | missense_variant | 6/9 | ENST00000347063.9 | NP_775933.2 | |
LOC105377499 | XR_007058334.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RNF175 | ENST00000347063.9 | c.533A>G | p.Asp178Gly | missense_variant | 6/9 | 1 | NM_173662.4 | ENSP00000340979 | P1 | |
ENST00000505051.1 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249124Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135152
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460830Hom.: 0 Cov.: 29 AF XY: 0.0000193 AC XY: 14AN XY: 726752
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152062Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74262
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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 | Aug 14, 2023 | The c.533A>G (p.D178G) alteration is located in exon 6 (coding exon 6) of the RNF175 gene. This alteration results from a A to G substitution at nucleotide position 533, causing the aspartic acid (D) at amino acid position 178 to be replaced by a glycine (G). 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
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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