Variant X-120109232-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_139282.3(RHOXF1):c.515G>A(p.Arg172His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0047 in 1,196,717 control chromosomes in the GnomAD database, including 32 homozygotes. There are 2,025 hemizygotes in GnomAD. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., 171 hem., cov: 22)

Exomes 𝑓: 0.0048 ( 28 hom. 1854 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.306

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:51582): (RHOXF1 antisense RNA 1)

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039516687).

BP6

Variant X-120109232-C-T is Benign according to our data. Variant chrX-120109232-C-T is described in ClinVar as [Benign]. Clinvar id is 715990.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00409 (455/111359) while in subpopulation EAS AF= 0.0269 (95/3528). AF 95% confidence interval is 0.0225. There are 4 homozygotes in gnomad4. There are 171 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOXF1	NM_139282.3 linkuse as main transcript	c.515G>A	p.Arg172His	missense_variant	3/3	ENST00000217999.3	NP_644811.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-11620C>T		intron_variant, non_coding_transcript_variant
RHOXF1	XM_011531281.3 linkuse as main transcript	c.599G>A	p.Arg200His	missense_variant	4/4		XP_011529583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.515G>A	p.Arg172His	missense_variant	3/3	1	NM_139282.3	ENSP00000217999	P1
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-11620C>T		intron_variant, non_coding_transcript_variant		2
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.515G>A	p.Arg172His	missense_variant	9/9			ENSP00000515423	P1

Frequencies

GnomAD3 genomes

AF:

0.00406

AC:

452

AN:

111306

Hom.:

Cov.:

AF XY:

0.00508

AC XY:

170

AN XY:

33486

show subpopulations

Gnomad AFR

AF:

0.000294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00191

Gnomad ASJ

AF:

0.000379

Gnomad EAS

AF:

0.0266

Gnomad SAS

AF:

0.0210

Gnomad FIN

AF:

0.0216

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00258

Gnomad OTH

AF:

0.00535

GnomAD3 exomes

AF:

0.00805

AC:

1464

AN:

181851

Hom.:

AF XY:

0.00862

AC XY:

572

AN XY:

66351

show subpopulations

Gnomad AFR exome

AF:

0.000383

Gnomad AMR exome

AF:

0.000517

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0331

Gnomad SAS exome

AF:

0.0201

Gnomad FIN exome

AF:

0.0225

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00476

AC:

5165

AN:

1085358

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

1854

AN XY:

352704

show subpopulations

Gnomad4 AFR exome

AF:

0.000381

Gnomad4 AMR exome

AF:

0.000542

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0300

Gnomad4 SAS exome

AF:

0.0181

Gnomad4 FIN exome

AF:

0.0202

Gnomad4 NFE exome

AF:

0.00265

Gnomad4 OTH exome

AF:

0.00580

GnomAD4 genome

AF:

0.00409

AC:

455

AN:

111359

Hom.:

Cov.:

AF XY:

0.00510

AC XY:

171

AN XY:

33549

show subpopulations

Gnomad4 AFR

AF:

0.000293

Gnomad4 AMR

AF:

0.00191

Gnomad4 ASJ

AF:

0.000379

Gnomad4 EAS

AF:

0.0269

Gnomad4 SAS

AF:

0.0206

Gnomad4 FIN

AF:

0.0216

Gnomad4 NFE

AF:

0.00258

Gnomad4 OTH

AF:

0.00726

Alfa

AF:

0.00421

Hom.:

154

Bravo

AF:

0.00265

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00149

AC:

ExAC

AF:

0.00850

AC:

1032

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.13

DANN

Benign

0.88

DEOGEN2

Benign

0.030

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0040

MetaSVM

Benign

-0.78

MutationAssessor

Benign

-0.24

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.79

REVEL

Benign

0.20

Sift

Benign

0.18

Sift4G

Benign

0.14

Polyphen

0.0010

Vest4

0.0040

MVP

0.14

MPC

0.26

ClinPred

0.0013

GERP RS

-1.7

Varity_R

0.022

gMVP

0.30

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