Menu
GeneBe

6-32178588-A-G

Variant summary

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

The NM_006913.4(RNF5):c.77A>G(p.Glu26Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000822 in 1,459,190 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: not found (cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RNF5
NM_006913.4 missense

Scores

7
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.16
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, 0.8

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF5NM_006913.4 linkuse as main transcriptc.77A>G p.Glu26Gly missense_variant 1/6 ENST00000375094.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF5ENST00000375094.4 linkuse as main transcriptc.77A>G p.Glu26Gly missense_variant 1/61 NM_006913.4 P1
RNF5ENST00000487940.1 linkuse as main transcriptn.152A>G non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000492
AC:
12
AN:
244094
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133482
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000349
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1459190
Hom.:
0
Cov.:
32
AF XY:
0.00000689
AC XY:
5
AN XY:
725970
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000268
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000378
ExAC
AF:
0.0000427
AC:
5

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 GeneticsJul 14, 2021The c.77A>G (p.E26G) alteration is located in exon 1 (coding exon 1) of the RNF5 gene. This alteration results from a A to G substitution at nucleotide position 77, causing the glutamic acid (E) at amino acid position 26 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
Pathogenic
0.90
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.12
Cadd
Pathogenic
33
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.59
D
Eigen
Pathogenic
0.72
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Pathogenic
0.99
D
M_CAP
Benign
0.030
D
MetaRNN
Pathogenic
0.80
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Pathogenic
-6.5
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0010
D
Sift4G
Pathogenic
0.0010
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.51
Loss of catalytic residue at E26 (P = 0.0541);
MVP
0.71
MPC
1.8
ClinPred
0.81
D
GERP RS
4.4
Varity_R
0.53
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs758750126; hg19: chr6-32146365; API