Variant 9-122851153-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100588.3(RC3H2):c.3308A>C(p.His1103Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

RC3H2
NM_001100588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.47

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RC3H2	NM_001100588.3 linkuse as main transcript	c.3308A>C	p.His1103Pro	missense_variant	20/21	ENST00000357244.7
RC3H2	NM_001354482.2 linkuse as main transcript	c.3194A>C	p.His1065Pro	missense_variant	19/20
RC3H2	NM_001354479.2 linkuse as main transcript	c.3137A>C	p.His1046Pro	missense_variant	19/20
RC3H2	NM_001354478.2 linkuse as main transcript	c.3308A>C	p.His1103Pro	missense_variant	20/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RC3H2	ENST00000357244.7 linkuse as main transcript	c.3308A>C	p.His1103Pro	missense_variant	20/21	5	NM_001100588.3	P1	Q9HBD1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249570

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135400

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727234

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00000827

AC:

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 04, 2023

The c.3308A>C (p.H1103P) alteration is located in exon 20 (coding exon 19) of the RC3H2 gene. This alteration results from a A to C substitution at nucleotide position 3308, causing the histidine (H) at amino acid position 1103 to be replaced by a proline (P). 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

0.10

BayesDel_addAF

Uncertain

0.076

BayesDel_noAF

Benign

-0.11

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.022

T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.18

Sift4G

Benign

0.17

T;T

Polyphen

0.98

D;D

Vest4

0.59

MVP

0.83

MPC

0.73

ClinPred

0.62

GERP RS

5.9

Varity_R

0.27

gMVP

0.48

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