chr16-88697576-C-G

Variant names:

• chr16-88697576-C-G
• rs374693627
• NM_178841.4:c.706G>C

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61
• 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]

ENSG00000259813 (HGNC:):

ACMG classification

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

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.706G>C	p.Glu236Gln	missense	Exon 6 of 6	NP_849163.1	Q96A37-1
	RNF166	NM_001171815.2		c.463G>C	p.Glu155Gln	missense	Exon 5 of 5	NP_001165286.1	Q96A37-3
	RNF166	NM_001171816.2		c.379G>C	p.Glu127Gln	missense	Exon 6 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.706G>C	p.Glu236Gln	missense	Exon 6 of 6	ENSP00000326095.4	Q96A37-1
	RNF166	ENST00000956472.1		c.703G>C	p.Glu235Gln	missense	Exon 6 of 6	ENSP00000626531.1
	RNF166	ENST00000878562.1		c.691G>C	p.Glu231Gln	missense	Exon 6 of 6	ENSP00000548621.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152112 Hom.: 0 Cov.: 33

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: 20 AN: 154054 AF XY: 0.000172

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.: 0 Cov.: 30 AF XY: 0.000154 AC XY: 106 AN XY: 689320

African (AFR) AF: 0.000158 AC: 5 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35674

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25166

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35702

South Asian (SAS) AF: 0.000669 AC: 53 AN: 79198

European-Finnish (FIN) AF: 0.0000208 AC: 1 AN: 48086

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5674

European-Non Finnish (NFE) AF: 0.000109 AC: 118 AN: 1078544

Other (OTH) AF: 0.000138 AC: 8 AN: 57938

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152112 Hom.: 0 Cov.: 33 AF XY: 0.000135 AC XY: 10 AN XY: 74306

African (AFR) AF: 0.000217 AC: 9 AN: 41452

American (AMR) AF: 0.0000658 AC: 1 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000180 Hom.: 0

Bravo AF: 0.000159

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000237 AC: 1

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.000124 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.44
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.6
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.026	D
Polyphen		0.85	P
Vest4		0.22
MVP		0.10
MPC		0.24
ClinPred		0.14	T
GERP RS		4.7
Varity_R		0.42
gMVP		0.74
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs374693627; hg19: chr16-88763984;