Variant 2-101402608-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145664.2(RFX8):c.1073A>G(p.Gln358Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RFX8
NM_001145664.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

RFX8 (HGNC:37253): (regulatory factor X8) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

RFX8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20594433).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFX8	NM_001145664.2 linkuse as main transcript	c.1073A>G	p.Gln358Arg	missense_variant	11/12	ENST00000428343.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFX8	ENST00000428343.6 linkuse as main transcript	c.1073A>G	p.Gln358Arg	missense_variant	11/12	2	NM_001145664.2		Q6ZV50-3
RFX8	ENST00000646893.2 linkuse as main transcript	c.1412A>G	p.Gln471Arg	missense_variant	14/15			P1	Q6ZV50-1
RFX8	ENST00000646446.1 linkuse as main transcript	c.1286A>G	p.Gln429Arg	missense_variant	14/15
RFX8	ENST00000481179.5 linkuse as main transcript	c.*789A>G		3_prime_UTR_variant, NMD_transcript_variant	13/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399788

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690390

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1073A>G (p.Q358R) alteration is located in exon 11 (coding exon 10) of the RFX8 gene. This alteration results from a A to G substitution at nucleotide position 1073, causing the glutamine (Q) at amino acid position 358 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.056

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.49

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.55

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.1

.;.;N

REVEL

Benign

0.14

Sift

Uncertain

0.011

.;.;D

Sift4G

Uncertain

0.010

.;.;D

Polyphen

0.73

.;.;P

Vest4

0.16

MVP

0.11

MPC

.;.;4.87291396618E-4

ClinPred

0.65

GERP RS

5.2

gMVP

0.096

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