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GeneBe

6-32178647-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006913.4(RNF5):c.136T>C(p.Tyr46His) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,610,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

RNF5
NM_006913.4 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12
Variant links:
Genes affected
RNF5 (HGNC:10068): (ring finger protein 5) The protein encoded by this gene contains a RING finger, which is a motif known to be involved in protein-protein interactions. This protein is a membrane-bound ubiquitin ligase. It can regulate cell motility by targeting paxillin ubiquitination and altering the distribution and localization of paxillin in cytoplasm and cell focal adhesions. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.767

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF5NM_006913.4 linkuse as main transcriptc.136T>C p.Tyr46His missense_variant 1/6 ENST00000375094.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF5ENST00000375094.4 linkuse as main transcriptc.136T>C p.Tyr46His missense_variant 1/61 NM_006913.4 P1
RNF5ENST00000487940.1 linkuse as main transcriptn.211T>C non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
151928
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00000819
AC:
2
AN:
244306
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133450
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:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1458550
Hom.:
0
Cov.:
32
AF XY:
0.0000234
AC XY:
17
AN XY:
725572
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:
0.0000342
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
151928
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74216
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000588
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000499
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000850
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.00

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 GeneticsNov 18, 2022The c.136T>C (p.Y46H) alteration is located in exon 1 (coding exon 1) of the RNF5 gene. This alteration results from a T to C substitution at nucleotide position 136, causing the tyrosine (Y) at amino acid position 46 to be replaced by a histidine (H). 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
Pathogenic
0.99
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
Cadd
Pathogenic
32
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.51
D
Eigen
Pathogenic
0.73
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.019
T
MetaRNN
Pathogenic
0.77
D
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.9
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0020
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.68
MutPred
0.72
Gain of helix (P = 0.2294);
MVP
0.56
MPC
1.9
ClinPred
0.97
D
GERP RS
4.5
Varity_R
0.13
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs774393683; hg19: chr6-32146424; API