Variant rs747687105 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BS1BS2

The NM_001282116.2(RFX3):c.2105C>T(p.Ala702Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,608 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

RFX3
NM_001282116.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.28

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 -7 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000684 (10/1461608) while in subpopulation SAS AF= 0.000104 (9/86256). AF 95% confidence interval is 0.0000539. There are 1 homozygotes in gnomad4_exome. There are 8 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RFX3	NM_001282116.2 link	c.2105C>T	p.Ala702Val	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.2105C>T	p.Ala702Val	missense_variant	Exon 17 of 17	2	NM_001282116.2	ENSP00000482598.1		P48380-1
RFX3	ENST00000382004.7 link	c.2105C>T	p.Ala702Val	missense_variant	Exon 18 of 18	1		ENSP00000371434.3		P48380-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250496

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.091

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

.;D

M_CAP

Benign

0.0042

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.44

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.40

N;.

REVEL

Benign

0.11

Sift

Benign

0.30

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.063

B;B

Vest4

0.14

MutPred

0.13

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.11

MPC

0.19

ClinPred

0.20

GERP RS

5.6

Varity_R

0.11

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.54

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.54

Position offset: 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

Computational scores

Splicing

Publications

LitVar

Other links and lift over