Variant X-120163624-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_032498.3(RHOXF2):c.704A>G(p.Asp235Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.12 ( 2 hom., 7 hem., cov: 2)

Exomes 𝑓: 0.12 ( 501 hom. 4344 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2
NM_032498.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.229

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004940629).

BP6

Variant X-120163624-A-G is Benign according to our data. Variant chrX-120163624-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2247580.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2	NM_032498.3 linkuse as main transcript	c.704A>G	p.Asp235Gly	missense_variant	4/4	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.704A>G	p.Asp235Gly	missense_variant	4/4	1	NM_032498.3	ENSP00000360441.3		Q9BQY4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

611

AN:

5224

Hom.:

Cov.:

AF XY:

0.0323

AC XY:

AN XY:

186

FAILED QC

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.0313

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.0496

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.0469

Gnomad MID

AF:

0.113

Gnomad NFE

AF:

0.0614

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.199

AC:

3411

AN:

17120

Hom.:

AF XY:

0.0504

AC XY:

AN XY:

1528

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.320

Gnomad FIN exome

AF:

0.0702

Gnomad NFE exome

AF:

0.0963

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.119

AC:

28960

AN:

242458

Hom.:

501

Cov.:

AF XY:

0.0688

AC XY:

4344

AN XY:

63102

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.0565

Gnomad4 EAS exome

AF:

0.277

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.0704

Gnomad4 NFE exome

AF:

0.0884

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.117

AC:

610

AN:

5223

Hom.:

Cov.:

AF XY:

0.0374

AC XY:

AN XY:

187

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.0496

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.0469

Gnomad4 NFE

AF:

0.0614

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.0914

Hom.:

391

ExAC

AF:

0.0288

AC:

102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.1

DANN

Benign

0.27

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.73

MutationAssessor

Benign

-0.55

PrimateAI

Benign

0.30

PROVEAN

Benign

0.84

REVEL

Benign

0.15

Sift

Benign

0.91

Sift4G

Benign

0.46

Polyphen

0.0

Vest4

0.074

MPC

2.3

ClinPred

0.0000096

GERP RS

0.66

Varity_R

0.040

gMVP

0.049

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