8-33551082-C-G

Variant names:

• chr8-33551082-C-G
• NM_024787.3:c.232G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024787.3(RNF122):​c.232G>C​(p.Val78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,844 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RNF122 NM_024787.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

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]

ACMG classification

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=0.32940516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF122	NM_024787.3	c.232G>C	p.Val78Leu	missense_variant	Exon 4 of 6	ENST00000256257.2	NP_079063.2
RNF122	XM_017013846.2	c.160G>C	p.Val54Leu	missense_variant	Exon 4 of 6		XP_016869335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF122	ENST00000256257.2	c.232G>C	p.Val78Leu	missense_variant	Exon 4 of 6	1	NM_024787.3	ENSP00000256257.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

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 Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.232G>C (p.V78L) alteration is located in exon 4 (coding exon 4) of the RNF122 gene. This alteration results from a G to C substitution at nucleotide position 232, causing the valine (V) at amino acid position 78 to be replaced by a leucine (L). 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	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.075
Sift	Uncertain	0.027	D
Sift4G	Benign	0.34	T
Polyphen		0.96	D
Vest4		0.33
MutPred		0.28		Gain of ubiquitination at K75 (P = 0.0737);
MVP		0.61
MPC		0.41
ClinPred		0.61	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-33408600;