Variant 9-122855389-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001100588.3(RC3H2):c.2610C>G(p.Asp870Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 1,612,776 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00048 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RC3H2
NM_001100588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

RC3H2 (HGNC:21461): (ring finger and CCCH-type domains 2) Enables nucleic acid binding activity and ubiquitin protein ligase activity. Involved in protein polyubiquitination. Located in cell surface; intracellular membrane-bounded organelle; and membrane. [provided by Alliance of Genome Resources, Apr 2022]

RC3H2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014073819).

BS2

High AC in GnomAd at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RC3H2	NM_001100588.3 linkuse as main transcript	c.2610C>G	p.Asp870Glu	missense_variant	15/21	ENST00000357244.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RC3H2	ENST00000357244.7 linkuse as main transcript	c.2610C>G	p.Asp870Glu	missense_variant	15/21	5	NM_001100588.3	P1	Q9HBD1-1

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000241

AC:

AN:

249472

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135384

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1460524

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000666

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000479

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000237

Hom.:

Bravo

AF:

0.000646

ESP6500AA

AF:

0.00108

AC:

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.000257

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Sep 17, 2021

The c.2610C>G (p.D870E) alteration is located in exon 15 (coding exon 14) of the RC3H2 gene. This alteration results from a C to G substitution at nucleotide position 2610, causing the aspartic acid (D) at amino acid position 870 to be replaced by a glutamic acid (E). 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

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

Cadd

Benign

Dann

Benign

0.65

DEOGEN2

Benign

0.021

T;T;.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.013

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.39

N;N;N;.

MutationTaster

Benign

0.72

D;D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.38

N;N;N;N

REVEL

Benign

0.15

Sift4G

Benign

0.89

T;T;T;T

Polyphen

0.92

P;P;P;.

Vest4

0.058

MutPred

0.38

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;

MVP

0.46

MPC

0.72

ClinPred

0.033

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.53

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