Variant X-119870608-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006978.3(RNF113A):c.1006G>A(p.Asp336Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00893 in 1,204,870 control chromosomes in the GnomAD database, including 34 homozygotes. There are 3,344 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 4 hom., 206 hem., cov: 23)

Exomes 𝑓: 0.0091 ( 30 hom. 3138 hem. )

Consequence

RNF113A
NM_006978.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

RNF113A (HGNC:12974): (ring finger protein 113A) This intronless gene encodes a protein which contains a C3H1-type zinc finger domain and a C3HC4 Ring-type (Really Interesting New Gene-type) zinc finger domain. The Ring-type zinc finger domain is identified in various tumor suppressors, DNA repair genes and cytokine receptor-associated molecules, and is probably involved in mediating protein-protein interactions. [provided by RefSeq, May 2010]

RNF113A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045681596).

BP6

Variant X-119870608-C-T is Benign according to our data. Variant chrX-119870608-C-T is described in ClinVar as [Benign]. Clinvar id is 777317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-119870608-C-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF113A	NM_006978.3 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	1/1	ENST00000371442.4	NP_008909.1	O15541

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF113A	ENST00000371442.4 linkuse as main transcript	c.1006G>A	p.Asp336Asn	missense_variant	1/1	6	NM_006978.3	ENSP00000360497.2		O15541

Frequencies

GnomAD3 genomes

AF:

0.00689

AC:

770

AN:

111751

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

206

AN XY:

33927

show subpopulations

Gnomad AFR

AF:

0.00127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00719

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00795

GnomAD3 exomes

AF:

0.00813

AC:

1443

AN:

177541

Hom.:

AF XY:

0.00826

AC XY:

517

AN XY:

62591

show subpopulations

Gnomad AFR exome

AF:

0.00122

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00857

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0134

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00962

GnomAD4 exome

AF:

0.00914

AC:

9992

AN:

1093067

Hom.:

Cov.:

AF XY:

0.00874

AC XY:

3138

AN XY:

359139

show subpopulations

Gnomad4 AFR exome

AF:

0.000876

Gnomad4 AMR exome

AF:

0.00542

Gnomad4 ASJ exome

AF:

0.00872

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00867

GnomAD4 genome

AF:

0.00689

AC:

770

AN:

111803

Hom.:

Cov.:

AF XY:

0.00606

AC XY:

206

AN XY:

33989

show subpopulations

Gnomad4 AFR

AF:

0.00127

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00719

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00785

Alfa

AF:

0.0100

Hom.:

429

Bravo

AF:

0.00711

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.00969

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.00771

AC:

936

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.89

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

REVEL

Benign

0.094

Sift

Benign

0.081

Sift4G

Uncertain

0.058

Polyphen

0.72

Vest4

0.10

MVP

0.44

MPC

0.92

ClinPred

0.0066

GERP RS

0.083

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.067

gMVP

0.41

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