Variant X-120159294-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032498.3(RHOXF2):c.359G>A(p.Arg120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000758 in 1,094,968 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 3 hem., cov: 19)

Exomes 𝑓: 0.000076 ( 0 hom. 12 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2
NM_032498.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.04

Variant links:

Genes affected

RHOXF2 (HGNC:30011): (Rhox homeobox family member 2) This gene, which encodes a transcriptional repressor, is one of two paralogous X-linked homeobox-containing genes and is highly expressed in a variety of cancers. In addition, the encoded protein associates with the cell membrane and with microtubules, and is concentrated at the leading edge of migratory cells. [provided by RefSeq, Dec 2015]

RHOXF2 links:

RHOXF1 (HGNC:29993): (Rhox homeobox family member 1) This gene is a member of the PEPP subfamily of paired-like homoebox genes. The gene may be regulated by androgens and epigenetic mechanisms. The encoded nuclear protein is likely a transcription factor that may play a role in human reproduction. [provided by RefSeq, Dec 2012]

RHOXF1 links:

RHOXF1 (HGNC:):

RHOXF1 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=0.042799234).

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2	NM_032498.3 linkuse as main transcript	c.359G>A	p.Arg120His	missense_variant	2/4	ENST00000371388.5	NP_115887.1	Q9BQY4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2	ENST00000371388.5 linkuse as main transcript	c.359G>A	p.Arg120His	missense_variant	2/4	1	NM_032498.3	ENSP00000360441.3		Q9BQY4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111844

Hom.:

Cov.:

AF XY:

0.0000874

AC XY:

AN XY:

34312

FAILED QC

Gnomad AFR

AF:

0.0000971

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000933

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000247

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000160

AC:

AN:

149682

Hom.:

AF XY:

0.0000849

AC XY:

AN XY:

47106

show subpopulations

Gnomad AFR exome

AF:

0.000407

Gnomad AMR exome

AF:

0.000279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000832

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.000259

GnomAD4 exome

AF:

0.0000758

AC:

AN:

1094968

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

360772

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.000257

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000996

Gnomad4 SAS exome

AF:

0.0000560

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000726

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000152

AC:

AN:

111867

Hom.:

Cov.:

AF XY:

0.0000873

AC XY:

AN XY:

34359

show subpopulations

Gnomad4 AFR

AF:

0.0000970

Gnomad4 AMR

AF:

0.0000932

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000247

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000384

Hom.:

ExAC

AF:

0.000151

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

Nov 13, 2024

The c.359G>A (p.R120H) alteration is located in exon 2 (coding exon 2) of the RHOXF2 gene. This alteration results from a G to A substitution at nucleotide position 359, causing the arginine (R) at amino acid position 120 to be replaced by a histidine (H). 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

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.077

DANN

Benign

0.95

DEOGEN2

Benign

0.10

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.58

M_CAP

Benign

0.0099

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.67

REVEL

Benign

0.27

Sift

Benign

0.057

Sift4G

Benign

0.14

Polyphen

0.53

Vest4

0.063

MutPred

0.12

Loss of phosphorylation at S119 (P = 0.1023);

MVP

0.043

MPC

2.6

ClinPred

0.0089

GERP RS

-3.6

Varity_R

0.027

gMVP

0.23

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