chr8-33551388-T-C

Variant names:

• chr8-33551388-T-C
• NM_024787.3:c.184A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024787.3(RNF122):​c.184A>G​(p.Lys62Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF122 NM_024787.3 missense, splice_region
• Scores: Splicing: ADA: 0.6585
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.41
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024787.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF122	NM_024787.3	MANE Select	c.184A>G	p.Lys62Glu	missense splice_region	Exon 3 of 6	NP_079063.2	Q9H9V4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF122	ENST00000256257.2	TSL:1 MANE Select	c.184A>G	p.Lys62Glu	missense splice_region	Exon 3 of 6	ENSP00000256257.1	Q9H9V4
	RNF122	ENST00000933859.1		c.292A>G	p.Lys98Glu	missense splice_region	Exon 4 of 7	ENSP00000603918.1
	RNF122	ENST00000933858.1		c.184A>G	p.Lys62Glu	missense splice_region	Exon 3 of 6	ENSP00000603917.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.042	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.4
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.078
Sift	Uncertain	0.028	D
Sift4G	Benign	0.14	T
Polyphen		0.32	B
Vest4		0.64
MutPred		0.46		Loss of methylation at K62 (P = 0.0132)
MVP		0.49
MPC		0.63
ClinPred		0.63	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.88
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.66
dbscSNV1_RF	Benign	0.61
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr8-33408906;