4-153720281-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173662.4(RNF175):ā€‹c.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

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56
Variant links:
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]

Genome browser will be placed here

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
RNF175NM_173662.4 linkuse as main transcriptc.533A>G p.Asp178Gly missense_variant 6/9 ENST00000347063.9 NP_775933.2
LOC105377499XR_007058334.1 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RNF175ENST00000347063.9 linkuse as main transcriptc.533A>G p.Asp178Gly missense_variant 6/91 NM_173662.4 ENSP00000340979 P1Q8N4F7-1
ENST00000505051.1 linkuse as main transcript upstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152062
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249124
Hom.:
0
AF XY:
0.0000222
AC XY:
3
AN XY:
135152
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1460830
Hom.:
0
Cov.:
29
AF XY:
0.0000193
AC XY:
14
AN XY:
726752
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152062
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000828
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsAug 14, 2023The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Uncertain
0.031
T
BayesDel_noAF
Benign
-0.18
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
T;.
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.035
D
MetaRNN
Uncertain
0.57
D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.6
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-5.3
D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.72
P;.
Vest4
0.89
MVP
0.57
MPC
0.29
ClinPred
0.98
D
GERP RS
4.5
Varity_R
0.62
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766883578; hg19: chr4-154641433; API