rs1031049118

Variant names:

• chr16-88698523-C-A
• rs1031049118
• NM_178841.4:c.627G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88698523-C-A
• chr16-88698523-C-G
• chr16-88698523-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178841.4(RNF166):​c.627G>T​(p.Lys209Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNF166 NM_178841.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27807966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF166	NM_178841.4	c.627G>T	p.Lys209Asn	missense_variant	Exon 5 of 6	ENST00000312838.9	NP_849163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF166	ENST00000312838.9	c.627G>T	p.Lys209Asn	missense_variant	Exon 5 of 6	1	NM_178841.4	ENSP00000326095.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;.;.;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.94	D;.;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.41
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Benign	0.049
Sift	Benign	0.24	T;T;T;D;T
Sift4G	Uncertain	0.045	D;T;T;D;D
Polyphen		0.33	B;.;.;.;.
Vest4		0.62
MutPred		0.42		Loss of ubiquitination at K209 (P = 0.011);.;.;.;.;
MVP		0.24
MPC		0.82
ClinPred		0.99	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.75

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: rs1031049118; hg19: chr16-88764931;