NM_174903.6:c.232C>G

Variant names:

• chr16-1967807-C-G
• rs760660528
• NM_174903.6:c.232C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_174903.6(RNF151):​c.232C>G​(p.Arg78Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,456,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R78H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RNF151 NM_174903.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.14
• Publications: 1 publications found

Genes affected

RNF151 (HGNC:23235): (ring finger protein 151) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174903.6. 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
	RNF151	NM_174903.6	MANE Select	c.232C>G	p.Arg78Gly	missense	Exon 3 of 4	NP_777563.2
	RNF151	NM_001348711.2		c.150-66C>G		intron	N/A	NP_001335640.1	H3BNJ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF151	ENST00000569714.6	TSL:1 MANE Select	c.232C>G	p.Arg78Gly	missense	Exon 3 of 4	ENSP00000456566.1	Q2KHN1
	RNF151	ENST00000321392.4	TSL:1	c.229C>G	p.Arg77Gly	missense	Exon 2 of 3	ENSP00000325794.3	A0A0C4DFQ4
	RNF151	ENST00000569210.6	TSL:2	c.150-66C>G		intron	N/A	ENSP00000454886.1	H3BNJ8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456188 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723710

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25994

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 84996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109280

Other (OTH) AF: 0.00 AC: 0 AN: 60208

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	-0.0047	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.1
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.63
Sift	Uncertain	0.0050	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.86	P
Vest4		0.49
MutPred		0.52		Loss of MoRF binding (P = 0.0128)
MVP		0.85
MPC		0.37
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.38
gMVP		0.53

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

Other links and lift over

dbSNP: rs760660528; hg19: chr16-2017808;