Variant 9-3247951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002919.4(RFX3):c.2049G>A(p.Leu683Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,613,454 control chromosomes in the GnomAD database, including 2,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.066 ( 1108 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 912 hom. )

Consequence

RFX3
NM_002919.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.168

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 9-3247951-C-T is Benign according to our data. Variant chr9-3247951-C-T is described in ClinVar as [Benign]. Clinvar id is 3056824.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.168 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2 link	c.1968+81G>A		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.2049G>A	p.Leu683Leu	synonymous_variant	Exon 14 of 14	1		ENSP00000351574.2	P48380-2
RFX3	ENST00000617270.5 link	c.1968+81G>A		intron_variant	Intron 15 of 16	2	NM_001282116.2	ENSP00000482598.1	P48380-1
RFX3	ENST00000382004.7 link	c.1968+81G>A		intron_variant	Intron 16 of 17	1		ENSP00000371434.3	P48380-1
RFX3	ENST00000449234.1 link	c.363+81G>A		intron_variant	Intron 2 of 2	3		ENSP00000415594.1	H0Y7W5

Frequencies

GnomAD3 genomes

AF:

0.0660

AC:

10037

AN:

152044

Hom.:

1104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0259

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0118

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.0474

GnomAD3 exomes

AF:

0.0185

AC:

4628

AN:

250110

Hom.:

446

AF XY:

0.0142

AC XY:

1918

AN XY:

135282

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.0117

Gnomad ASJ exome

AF:

0.00785

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00856

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000584

Gnomad OTH exome

AF:

0.00769

GnomAD4 exome

AF:

0.00745

AC:

10891

AN:

1461290

Hom.:

912

Cov.:

AF XY:

0.00663

AC XY:

4817

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.0139

Gnomad4 ASJ exome

AF:

0.00773

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00962

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000318

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0661

AC:

10059

AN:

152164

Hom.:

1108

Cov.:

AF XY:

0.0638

AC XY:

4745

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.0258

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000750

Gnomad4 OTH

AF:

0.0469

Alfa

AF:

0.0209

Hom.:

110

Bravo

AF:

0.0749

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RFX3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 07, 2019

This variant is classified as 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_noAF

Benign

-0.80

CADD

Benign

5.5

DANN

Benign

0.56

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