Variant 9-3225104-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001282116.2(RFX3):c.2188G>A(p.Val730Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,613,946 control chromosomes in the GnomAD database, including 4 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00099 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 3 hom. )

Consequence

RFX3
NM_001282116.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.84

Variant links:

Genes affected

RFX3 (HGNC:9984): (regulatory factor X3) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X2, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. Multiple transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2013]

RFX3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005207628).

BP6

Variant 9-3225104-C-T is Benign according to our data. Variant chr9-3225104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042204.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000991 (151/152300) while in subpopulation NFE AF= 0.00129 (88/68030). AF 95% confidence interval is 0.00107. There are 1 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 151 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2 link	c.2188G>A	p.Val730Ile	missense_variant	Exon 17 of 17	ENST00000617270.5	NP_001269045.1	P48380-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFX3	ENST00000617270.5 link	c.2188G>A	p.Val730Ile	missense_variant	Exon 17 of 17	2	NM_001282116.2	ENSP00000482598.1		P48380-1
RFX3	ENST00000382004.7 link	c.2188G>A	p.Val730Ile	missense_variant	Exon 18 of 18	1		ENSP00000371434.3		P48380-1

Frequencies

GnomAD3 genomes

AF:

0.000992

AC:

151

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00129

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00120

AC:

300

AN:

250858

Hom.:

AF XY:

0.00119

AC XY:

162

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00504

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.00178

AC:

2596

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1236

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

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:

0.00521

Gnomad4 NFE exome

AF:

0.00203

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.000991

AC:

151

AN:

152300

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00443

Gnomad4 NFE

AF:

0.00129

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00138

Hom.:

Bravo

AF:

0.000790

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00103

AC:

125

EpiCase

AF:

0.00120

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RFX3-related disorder

Benign:1

Jan 08, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

0.027

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.92

.;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.0052

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.41

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.020

N;.

REVEL

Benign

0.061

Sift

Benign

0.039

D;.

Sift4G

Benign

0.98

T;T

Polyphen

0.13

B;B

Vest4

0.086

MVP

0.12

MPC

0.15

ClinPred

0.030

GERP RS

5.7

Varity_R

0.057

gMVP

0.056

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