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

Variant summary

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

The NM_002919.4(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
NM_002919.4 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 -13 ACMG points.

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.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000289 (44/152192) while in subpopulation NFE AF= 0.000382 (26/68036). AF 95% confidence interval is 0.000267. There are 0 homozygotes in gnomad4. There are 25 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2 link	c.1968+60C>G		intron_variant	Intron 15 of 16	ENST00000617270.5	NP_001269045.1	P48380-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RFX3	ENST00000358730.6 link	c.2028C>G	p.His676Gln	missense_variant	Exon 14 of 14	1		ENSP00000351574.2	P48380-2
RFX3	ENST00000617270.5 link	c.1968+60C>G		intron_variant	Intron 15 of 16	2	NM_001282116.2	ENSP00000482598.1	P48380-1
RFX3	ENST00000382004.7 link	c.1968+60C>G		intron_variant	Intron 16 of 17	1		ENSP00000371434.3	P48380-1
RFX3	ENST00000449234.1 link	c.363+60C>G		intron_variant	Intron 2 of 2	3		ENSP00000415594.1	H0Y7W5

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

May 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

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

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