8-33558670-C-T

Variant summary

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

The NM_024787.3(RNF122):​c.127G>A​(p.Gly43Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,611,744 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

RNF122
NM_024787.3 missense

Scores

4
4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNF122NM_024787.3 linkc.127G>A p.Gly43Ser missense_variant Exon 2 of 6 ENST00000256257.2 NP_079063.2 Q9H9V4
RNF122XM_017013846.2 linkc.55G>A p.Gly19Ser missense_variant Exon 2 of 6 XP_016869335.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNF122ENST00000256257.2 linkc.127G>A p.Gly43Ser missense_variant Exon 2 of 6 1 NM_024787.3 ENSP00000256257.1 Q9H9V4

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152102
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250874
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135602
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000581
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000329
AC:
48
AN:
1459642
Hom.:
0
Cov.:
29
AF XY:
0.0000399
AC XY:
29
AN XY:
726182
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
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:
0.0000378
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152102
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74290
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.127G>A (p.G43S) alteration is located in exon 2 (coding exon 2) of the RNF122 gene. This alteration results from a G to A substitution at nucleotide position 127, causing the glycine (G) at amino acid position 43 to be replaced by a serine (S). 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
0.74
BayesDel_addAF
Benign
-0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.021
T
Eigen
Uncertain
0.43
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.96
D
M_CAP
Benign
0.023
T
MetaRNN
Pathogenic
0.78
D
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
2.0
M
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.18
Sift
Benign
0.14
T
Sift4G
Benign
0.076
T
Polyphen
1.0
D
Vest4
0.81
MutPred
0.61
Gain of helix (P = 0.0854);
MVP
0.63
MPC
1.2
ClinPred
0.88
D
GERP RS
4.5
Varity_R
0.10
gMVP
0.92

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: rs759595318; hg19: chr8-33416188; API