Variant chrX-120115546-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_139282.3(RHOXF1):c.317G>C(p.Arg106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,024,578 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.000013 ( 0 hom. 1 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.20

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28351003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF1	NM_139282.3 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	1/3	ENST00000217999.3	NP_644811.1	Q8NHV9
RHOXF1	XM_011531281.3 linkuse as main transcript	c.401G>C	p.Arg134Pro	missense_variant	2/4		XP_011529583.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-5306C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	1/3	1	NM_139282.3	ENSP00000217999.1	Q8NHV9
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.317G>C	p.Arg106Pro	missense_variant	7/9			ENSP00000515423.1	Q8NHV9
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-5306C>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

125003

Hom.:

AF XY:

0.0000247

AC XY:

AN XY:

40523

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000127

AC:

AN:

1024578

Hom.:

Cov.:

AF XY:

0.00000305

AC XY:

AN XY:

328014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000149

Gnomad4 OTH exome

AF:

0.0000234

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

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

Nov 24, 2024

The c.317G>C (p.R106P) alteration is located in exon 1 (coding exon 1) of the RHOXF1 gene. This alteration results from a G to C substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 to be replaced by a proline (P). 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

0.21

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.014

DANN

Benign

0.61

DEOGEN2

Benign

0.37

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.49

M_CAP

Benign

0.011

MetaRNN

Benign

0.28

MetaSVM

Uncertain

-0.081

MutationAssessor

Benign

-0.59

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.41

Sift

Benign

0.21

Sift4G

Benign

0.12

Polyphen

0.93

Vest4

0.10

MutPred

0.42

Gain of glycosylation at R106 (P = 0.0044);

MVP

0.60

MPC

0.38

ClinPred

0.51

GERP RS

-5.5

Varity_R

0.20

gMVP

0.71

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