Variant 9-3247972-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBP6BS2

The ENST00000358730.6(RFX3):c.2028C>G(p.His676Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,613,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

RFX3
ENST00000358730.6 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.653

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 -8 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), RFX3. . Gene score misZ 3.4728 (greater than the threshold 3.09). Trascript score misZ 3.1046 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder, autism spectrum disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.005157888).

BP6

Variant 9-3247972-G-C is Benign according to our data. Variant chr9-3247972-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3357140.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFX3	NM_001282116.2 linkuse as main transcript	c.1968+60C>G		intron_variant		ENST00000617270.5	NP_001269045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFX3	ENST00000358730.6 linkuse as main transcript	c.2028C>G	p.His676Gln	missense_variant	14/14	1		ENSP00000351574		P48380-2
RFX3	ENST00000617270.5 linkuse as main transcript	c.1968+60C>G		intron_variant		2	NM_001282116.2	ENSP00000482598	P1	P48380-1
RFX3	ENST00000382004.7 linkuse as main transcript	c.1968+60C>G		intron_variant		1		ENSP00000371434	P1	P48380-1
RFX3	ENST00000449234.1 linkuse as main transcript	c.363+60C>G		intron_variant		3		ENSP00000415594

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000423

AC:

106

AN:

250576

Hom.:

AF XY:

0.000458

AC XY:

AN XY:

135462

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.000371

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000268

AC:

392

AN:

1461606

Hom.:

Cov.:

AF XY:

0.000278

AC XY:

202

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000807

Gnomad4 NFE exome

AF:

0.000196

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000289

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000282

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000752

Hom.:

Bravo

AF:

0.000200

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RFX3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2024

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

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.45

DANN

Benign

0.78

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.22

M_CAP

Benign

0.022

MetaRNN

Benign

0.0052

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

0.60

REVEL

Benign

0.0090

Sift

Pathogenic

0.0

Sift4G

Benign

0.96

Polyphen

0.0

Vest4

0.11

MutPred

0.24

Loss of loop (P = 0.0512);

MVP

0.10

ClinPred

0.016

GERP RS

-2.8

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