Variant 2-85595788-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016494.4(RNF181):c.25G>A(p.Asp9Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

RNF181
NM_016494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.12

Variant links:

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]

RNF181 links:

RNF181 (HGNC:):

RNF181 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18422711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF181	NM_016494.4 linkuse as main transcript	c.25G>A	p.Asp9Asn	missense_variant	1/5	ENST00000306368.9	NP_057578.1	Q9P0P0
RNF181	XM_005264359.5 linkuse as main transcript	c.25G>A	p.Asp9Asn	missense_variant	1/4		XP_005264416.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF181	ENST00000306368.9 linkuse as main transcript	c.25G>A	p.Asp9Asn	missense_variant	1/5	1	NM_016494.4	ENSP00000306906.4		Q9P0P0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250380

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135686

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:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000477

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2024

The c.25G>A (p.D9N) alteration is located in exon 1 (coding exon 1) of the RNF181 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the aspartic acid (D) at amino acid position 9 to be replaced by an asparagine (N). 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

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0088

T;T;.

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

0.66

.;N;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.32

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.67

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0020

.;B;.

Vest4

0.21

MVP

0.60

MPC

0.21

ClinPred

0.24

GERP RS

4.5

Varity_R

0.10

gMVP

0.50

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

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