Variant chrX-120077121-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001099685.3(RHOXF2B):c.247G>A(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000643 in 964,456 control chromosomes in the GnomAD database, including 10 homozygotes. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 1 hom., 0 hem., cov: 14)

Exomes 𝑓: 0.000064 ( 10 hom. 13 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2B
NM_001099685.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.74

Variant links:

Genes affected

RHOXF2B (HGNC:33519): (Rhox homeobox family member 2B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in positive regulation of gene expression. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

RHOXF2B links:

RHOXF1-AS1 (HGNC:):

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.020706534).

BS2

High Homozygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2B	NM_001099685.3 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	2/4	ENST00000371402.5	NP_001093155.1	P0C7M4
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.297+40589C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2B	ENST00000371402.5 linkuse as main transcript	c.247G>A	p.Ala83Thr	missense_variant	2/4	1	NM_001099685.3	ENSP00000360455.3		P0C7M4
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.297+40589C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

85769

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20189

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000909

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000454

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

152100

Hom.:

AF XY:

0.0000206

AC XY:

AN XY:

48646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000500

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000396

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000142

Gnomad OTH exome

AF:

0.000260

GnomAD4 exome

AF:

0.0000643

AC:

AN:

964456

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

275334

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000921

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000637

Gnomad4 OTH exome

AF:

0.0000496

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000466

AC:

AN:

85769

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

20189

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000909

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000454

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

ExAC

AF:

0.000108

AC:

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

Apr 25, 2023

The c.247G>A (p.A83T) alteration is located in exon 2 (coding exon 2) of the RHOXF2B gene. This alteration results from a G to A substitution at nucleotide position 247, causing the alanine (A) at amino acid position 83 to be replaced by a threonine (T). 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

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.022

DANN

Benign

0.95

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.27

M_CAP

Benign

0.0079

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.26

PrimateAI

Benign

0.36

PROVEAN

Benign

0.77

REVEL

Benign

0.14

Sift

Benign

0.89

Sift4G

Benign

0.76

Polyphen

0.0

Vest4

0.066

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0082);

MVP

0.043

MPC

1.8

ClinPred

0.0098

GERP RS

-0.17

Varity_R

0.026

gMVP

0.070

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