Variant X-120159345-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 ENST00000371388.5(RHOXF2):c.410A>G(p.Asn137Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. N137N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., 0 hem., cov: 19)

Exomes 𝑓: 0.000015 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2
ENST00000371388.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.52

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=0.036122978).

BP6

Variant X-120159345-A-G is Benign according to our data. Variant chrX-120159345-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3314249.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.410A>G	p.Asn137Ser	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.410A>G	p.Asn137Ser	missense_variant	2/4	1	NM_032498.3	ENSP00000360441.3		Q9BQY4

Frequencies

GnomAD3 genomes

AF:

0.0000442

AC:

AN:

113123

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35249

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000925

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000550

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

177110

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000146

AC:

AN:

1096367

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

361933

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000995

Gnomad4 SAS exome

AF:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000239

GnomAD4 genome

AF:

0.0000442

AC:

AN:

113123

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35249

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000925

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000550

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00131

Alfa

AF:

0.0000959

Hom.:

ExAC

AF:

0.00000825

AC:

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

May 24, 2024

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

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0040

DANN

Benign

0.22

DEOGEN2

Benign

0.072

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.38

M_CAP

Benign

0.0058

MetaRNN

Benign

0.036

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.11

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.25

Sift

Benign

0.31

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.10

MutPred

0.40

Loss of catalytic residue at N137 (P = 0.1312);

MVP

0.043

MPC

1.6

ClinPred

0.042

GERP RS

-4.2

Varity_R

0.034

gMVP

0.063

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