Variant 16-88706196-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000312838.9(RNF166):c.130G>T(p.Val44Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000286 in 1,298,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

RNF166
ENST00000312838.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.61

Variant links:

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]

RNF166 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF166	NM_178841.4 linkuse as main transcript	c.130G>T	p.Val44Leu	missense_variant	1/6	ENST00000312838.9	NP_849163.1	Q96A37-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNF166	ENST00000312838.9 linkuse as main transcript	c.130G>T	p.Val44Leu	missense_variant	1/6	1	NM_178841.4	ENSP00000326095.4	Q96A37-1
RNF166	ENST00000562544.1 linkuse as main transcript	c.67G>T	p.Val23Leu	missense_variant	1/4	5		ENSP00000455539.1	H3BPZ9
RNF166	ENST00000567844.1 linkuse as main transcript	c.114+16G>T		intron_variant		5		ENSP00000457336.1	Q96A37-3

Frequencies

GnomAD3 genomes

AF:

0.000153

AC:

AN:

150288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

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:

0.000267

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000592

AC:

AN:

50642

Hom.:

AF XY:

0.0000970

AC XY:

AN XY:

30914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000304

AC:

349

AN:

1148420

Hom.:

Cov.:

AF XY:

0.000302

AC XY:

170

AN XY:

562388

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000688

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:

0.000355

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000153

AC:

AN:

150288

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73360

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000267

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000212

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.130G>T (p.V44L) alteration is located in exon 1 (coding exon 1) of the RNF166 gene. This alteration results from a G to T substitution at nucleotide position 130, causing the valine (V) at amino acid position 44 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

0.078

Eigen_PC

Benign

0.066

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.68

T;T

M_CAP

Pathogenic

1.0

MetaRNN

Uncertain

0.55

D;D

MetaSVM

Uncertain

-0.068

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.61

Sift

Benign

0.11

T;D

Sift4G

Uncertain

0.037

D;T

Polyphen

0.66

P;.

Vest4

0.55

MutPred

0.49

Gain of relative solvent accessibility (P = 0.09);.;

MVP

0.84

MPC

0.44

ClinPred

0.19

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.21

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over