rs144508728

Variant names:

• chr16-88699654-C-G
• rs144508728
• NM_178841.4:c.391G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88699654-C-G
• chr16-88699654-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178841.4(RNF166):​c.391G>C​(p.Val131Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign 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. V131I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RNF166 NM_178841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10
• Publications: 0 publications found

Genes affected

RNF166 (HGNC:28856): (ring finger protein 166) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19799334).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178841.4. 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
	RNF166	NM_178841.4	MANE Select	c.391G>C	p.Val131Leu	missense	Exon 3 of 6	NP_849163.1	Q96A37-1
	RNF166	NM_001171815.2		c.148G>C	p.Val50Leu	missense	Exon 2 of 5	NP_001165286.1	Q96A37-3
	RNF166	NM_001171816.2		c.64G>C	p.Val22Leu	missense	Exon 3 of 6	NP_001165287.1	Q96A37-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF166	ENST00000312838.9	TSL:1 MANE Select	c.391G>C	p.Val131Leu	missense	Exon 3 of 6	ENSP00000326095.4	Q96A37-1
	RNF166	ENST00000956472.1		c.391G>C	p.Val131Leu	missense	Exon 3 of 6	ENSP00000626531.1
	RNF166	ENST00000878562.1		c.391G>C	p.Val131Leu	missense	Exon 3 of 6	ENSP00000548621.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461110 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726856

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111844

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.034
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.1
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.074
Sift	Benign	0.056	T
Sift4G	Benign	0.074	T
Polyphen		0.25	B
Vest4		0.54
MutPred		0.46		Loss of disorder (P = 0.1982)
MVP		0.19
MPC		0.26
ClinPred		0.97	D
GERP RS		4.6
PromoterAI		-0.0037	Neutral
Varity_R		0.14
gMVP		0.39
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs144508728; hg19: chr16-88766062;