Variant X-120109219-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139282.3(RHOXF1):c.528C>A(p.Asp176Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,190,957 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000024 ( 0 hom. 13 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.14

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039613515).

BS2

High Hemizygotes in GnomAdExome4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF1	NM_139282.3 linkuse as main transcript	c.528C>A	p.Asp176Glu	missense_variant	3/3	ENST00000217999.3	NP_644811.1	Q8NHV9
RHOXF1	XM_011531281.3 linkuse as main transcript	c.612C>A	p.Asp204Glu	missense_variant	4/4		XP_011529583.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-11633G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.528C>A	p.Asp176Glu	missense_variant	3/3	1	NM_139282.3	ENSP00000217999.1	Q8NHV9
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.528C>A	p.Asp176Glu	missense_variant	9/9			ENSP00000515423.1	Q8NHV9
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-11633G>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111426

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33608

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:

0.000281

Gnomad SAS

AF:

0.000379

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000385

AC:

AN:

181645

Hom.:

AF XY:

0.0000302

AC XY:

AN XY:

66143

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000362

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000241

AC:

AN:

1079478

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

347716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000167

Gnomad4 SAS exome

AF:

0.000287

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111479

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33671

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.000380

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000330

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

Oct 02, 2023

The c.528C>A (p.D176E) alteration is located in exon 3 (coding exon 3) of the RHOXF1 gene. This alteration results from a C to A substitution at nucleotide position 528, causing the aspartic acid (D) at amino acid position 176 to be replaced by a glutamic acid (E). 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

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0090

DANN

Benign

0.76

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.34

M_CAP

Benign

0.027

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.99

PrimateAI

Benign

0.30

PROVEAN

Benign

0.34

REVEL

Benign

0.18

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.026

Vest4

0.022

MutPred

0.36

Gain of phosphorylation at Y180 (P = 0.2617);

MVP

0.21

MPC

0.29

ClinPred

0.023

GERP RS

-6.3

Varity_R

0.081

gMVP

0.18

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