Genetic Variant RNF166:p.Glu236Gln (chr16-88697576-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_178841.4(RNF166):c.706G>C(p.Glu236Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,549,692 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: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

RNF166
NM_178841.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

Publications

0 publications found

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:

ENSG00000259813 (HGNC:):

ENSG00000259813 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF166	NM_178841.4 link	c.706G>C	p.Glu236Gln	missense_variant	Exon 6 of 6	ENST00000312838.9	NP_849163.1	Q96A37-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF166	ENST00000312838.9 link	c.706G>C	p.Glu236Gln	missense_variant	Exon 6 of 6	1	NM_178841.4	ENSP00000326095.4		Q96A37-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000130

AC:

AN:

154054

AF XY:

0.000172

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000121

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000135

AC:

188

AN:

1397580

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

106

AN XY:

689320

show subpopulations

African (AFR)

AF:

0.000158

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.0000397

AC:

AN:

25166

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35702

South Asian (SAS)

AF:

0.000669

AC:

AN:

79198

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48086

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.000109

AC:

118

AN:

1078544

Other (OTH)

AF:

0.000138

AC:

AN:

57938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000105

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41452

American (AMR)

AF:

0.0000658

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000237

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000124

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.706G>C (p.E236Q) alteration is located in exon 6 (coding exon 6) of the RNF166 gene. This alteration results from a G to C substitution at nucleotide position 706, causing the glutamic acid (E) at amino acid position 236 to be replaced by a glutamine (Q). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.44

CADD

Pathogenic

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.062

T;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;.;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;.;.

PhyloP100

5.6

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.026

D;D;D;T

Polyphen

0.85

P;.;.;.

Vest4

0.22

MVP

0.10

MPC

0.24

ClinPred

0.14

GERP RS

4.7

Varity_R

0.42

gMVP

0.74

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.44

Position offset: -3

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

Publications

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16-88697576-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over