Variant X-120109268-C-T 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.479G>A(p.Arg160Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000756 in 1,191,108 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000065 ( 0 hom. 0 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.771

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 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=0.40336376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOXF1	NM_139282.3 linkuse as main transcript	c.479G>A	p.Arg160Gln	missense_variant	3/3	ENST00000217999.3	NP_644811.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-11584C>T		intron_variant, non_coding_transcript_variant
RHOXF1	XM_011531281.3 linkuse as main transcript	c.563G>A	p.Arg188Gln	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.479G>A	p.Arg160Gln	missense_variant	3/3	1	NM_139282.3	ENSP00000217999	P1
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-11584C>T		intron_variant, non_coding_transcript_variant		2
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.479G>A	p.Arg160Gln	missense_variant	9/9			ENSP00000515423	P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111469

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33633

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000955

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000110

AC:

AN:

181901

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66401

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000726

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000648

AC:

AN:

1079639

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

347453

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000668

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000483

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111469

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33633

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.0000955

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Dec 28, 2023

The c.479G>A (p.R160Q) alteration is located in exon 3 (coding exon 3) of the RHOXF1 gene. This alteration results from a G to A substitution at nucleotide position 479, causing the arginine (R) at amino acid position 160 to be replaced by a glutamine (Q). 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

0.29

BayesDel_addAF

Uncertain

0.082

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

FATHMM_MKL

Benign

0.0070

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.45

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.40

Sift

Uncertain

0.0090

Sift4G

Benign

0.063

Polyphen

1.0

Vest4

0.20

MutPred

0.61

Loss of MoRF binding (P = 0.0627);

MVP

0.60

MPC

0.76

ClinPred

0.68

GERP RS

2.3

Varity_R

0.085

gMVP

0.62

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