Variant X-120109203-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000217999.3(RHOXF1):c.544G>A(p.Val182Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000382 in 1,178,817 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000039 ( 0 hom. 12 hem. )

Consequence

RHOXF1
ENST00000217999.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

Variant links:

Genes affected

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-AS1 (HGNC:):

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027217299).

BP6

Variant X-120109203-C-T is Benign according to our data. Variant chrX-120109203-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3154122.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF1	NM_139282.3 linkuse as main transcript	c.544G>A	p.Val182Ile	missense_variant	3/3	ENST00000217999.3	NP_644811.1	Q8NHV9
RHOXF1	XM_011531281.3 linkuse as main transcript	c.628G>A	p.Val210Ile	missense_variant	4/4		XP_011529583.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-11649C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.544G>A	p.Val182Ile	missense_variant	3/3	1	NM_139282.3	ENSP00000217999.1	Q8NHV9
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.544G>A	p.Val182Ile	missense_variant	9/9			ENSP00000515423.1	Q8NHV9
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-11649C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111500

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33674

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000612

AC:

AN:

179861

Hom.:

AF XY:

0.0000620

AC XY:

AN XY:

64483

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000373

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000583

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000248

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000394

AC:

AN:

1067317

Hom.:

Cov.:

AF XY:

0.0000354

AC XY:

AN XY:

338527

show subpopulations

Gnomad4 AFR exome

AF:

0.0000770

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000404

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111500

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33674

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000577

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

Mar 05, 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

0.099

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.0010

DANN

Benign

0.77

DEOGEN2

Benign

0.016

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.24

M_CAP

Benign

0.012

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.050

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.030

REVEL

Benign

0.23

Sift

Benign

0.64

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.051

MutPred

0.54

Loss of catalytic residue at V182 (P = 0.0731);

MVP

0.26

MPC

0.17

ClinPred

0.015

GERP RS

-6.3

Varity_R

0.031

gMVP

0.14

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