8-33551364-C-T

Variant summary

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

The NM_024787.3(RNF122):​c.208G>A​(p.Glu70Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNF122
NM_024787.3 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23
Variant links:
Genes affected
RNF122 (HGNC:21147): (ring finger protein 122) The encoded protein contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. The encoded protein is localized to the endoplasmic reticulum and golgi apparatus, and may be associated with cell viability. [provided by RefSeq, Jul 2013]

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 rank MANE Protein UniProt
RNF122NM_024787.3 linkc.208G>A p.Glu70Lys missense_variant Exon 3 of 6 ENST00000256257.2 NP_079063.2 Q9H9V4
RNF122XM_017013846.2 linkc.136G>A p.Glu46Lys missense_variant Exon 3 of 6 XP_016869335.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF122ENST00000256257.2 linkc.208G>A p.Glu70Lys missense_variant Exon 3 of 6 1 NM_024787.3 ENSP00000256257.1 Q9H9V4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152184
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461780
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74342
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.208G>A (p.E70K) alteration is located in exon 3 (coding exon 3) of the RNF122 gene. This alteration results from a G to A substitution at nucleotide position 208, causing the glutamic acid (E) at amino acid position 70 to be replaced by a lysine (K). 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
0.25
BayesDel_addAF
Benign
0.0058
T
BayesDel_noAF
Benign
-0.23
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.034
T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.0091
T
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
PrimateAI
Pathogenic
0.80
D
PROVEAN
Benign
-0.89
N
REVEL
Benign
0.13
Sift
Benign
0.038
D
Sift4G
Benign
0.10
T
Polyphen
0.98
D
Vest4
0.63
MutPred
0.37
Gain of MoRF binding (P = 0.0081);
MVP
0.45
MPC
0.48
ClinPred
0.80
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.27
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.30
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.30
Position offset: 3

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: rs1187595782; hg19: chr8-33408882; API