chr4-153712556-C-T

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

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94
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 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
RNF175NM_173662.4 linkuse as main transcriptc.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
RNF175ENST00000347063.9 linkuse as main transcriptc.785G>A p.Arg262Gln missense_variant 8/91 NM_173662.4 ENSP00000340979 P1Q8N4F7-1
RNF175ENST00000513656.5 linkuse as main transcriptc.*532G>A 3_prime_UTR_variant, NMD_transcript_variant 7/73 ENSP00000421761

Frequencies

GnomAD3 genomes
AF:
0.000184
AC:
28
AN:
152154
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000652
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000605
AC:
15
AN:
247866
Hom.:
0
AF XY:
0.0000446
AC XY:
6
AN XY:
134452
show subpopulations
Gnomad AFR exome
AF:
0.000844
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:
0.00000890
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1460146
Hom.:
0
Cov.:
29
AF XY:
0.0000234
AC XY:
17
AN XY:
726374
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.000184
AC:
28
AN:
152272
Hom.:
0
Cov.:
33
AF XY:
0.000201
AC XY:
15
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.000650
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000326
Hom.:
0
Bravo
AF:
0.000159
ESP6500AA
AF:
0.00104
AC:
4
ESP6500EA
AF:
0.000121
AC:
1
ExAC
AF:
0.0000828
AC:
10

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 GeneticsDec 03, 2021The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.5
L
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0050
D
Polyphen
1.0
D
Vest4
0.73
MVP
0.42
MPC
0.26
ClinPred
0.45
T
GERP RS
3.0
Varity_R
0.66
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs200984268; hg19: chr4-154633708; API