2-85595798-C-T

Variant names:

• chr2-85595798-C-T
• rs765575244
• NM_016494.4:c.35C>T

Variant summary

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

The NM_016494.4(RNF181):​c.35C>T​(p.Pro12Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RNF181 NM_016494.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.66
• Publications: 1 publications found

Genes affected

RNF181 (HGNC:28037): (ring finger protein 181) RNF181 binds the integrin alpha-IIb (ITGA2B; MIM 607759)/beta-3 (ITGB3; MIM 173470) complex and has E3 ubiquitin ligase activity (Brophy et al., 2008 [PubMed 18331836]).[supplied by OMIM, Dec 2008]

ENSG00000288858 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016494.4. 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
	RNF181	NM_016494.4	MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 1 of 5	NP_057578.1	Q9P0P0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF181	ENST00000306368.9	TSL:1 MANE Select	c.35C>T	p.Pro12Leu	missense	Exon 1 of 5	ENSP00000306906.4	Q9P0P0
	RNF181	ENST00000867201.1		c.35C>T	p.Pro12Leu	missense	Exon 1 of 5	ENSP00000537260.1
	RNF181	ENST00000923728.1		c.35C>T	p.Pro12Leu	missense	Exon 1 of 5	ENSP00000593787.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250426 AF XY: 0.00000737

Gnomad AFR exome AF: 0.0000620

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

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	Benign	0.15
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.085
Eigen_PC	Benign	-0.033
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	0.28	D
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.36
Sift	Benign	0.14	T
Sift4G	Uncertain	0.016	D
Polyphen		0.015	B
Vest4		0.18
MutPred		0.26		Loss of loop (P = 0.0128)
MVP		0.70
MPC		0.26
ClinPred		0.94	D
GERP RS		4.4
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.74
Mutation Taster		=84/16	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: rs765575244; hg19: chr2-85822921;