chrX-120159217-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_032498.3(RHOXF2):​c.282C>T​(p.Leu94Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,205,265 control chromosomes in the GnomAD database, including 8 homozygotes. There are 234 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., 7 hem., cov: 19)
Exomes 𝑓: 0.0012 ( 8 hom. 227 hem. )

Consequence

RHOXF2
NM_032498.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.86
Variant links:
Genes affected
RHOXF2 (HGNC:30011): (Rhox homeobox family member 2) This gene, which encodes a transcriptional repressor, is one of two paralogous X-linked homeobox-containing genes and is highly expressed in a variety of cancers. In addition, the encoded protein associates with the cell membrane and with microtubules, and is concentrated at the leading edge of migratory cells. [provided by RefSeq, Dec 2015]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant X-120159217-C-T is Benign according to our data. Variant chrX-120159217-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661316.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.86 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHOXF2NM_032498.3 linkc.282C>T p.Leu94Leu synonymous_variant Exon 2 of 4 ENST00000371388.5 NP_115887.1 Q9BQY4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOXF2ENST00000371388.5 linkc.282C>T p.Leu94Leu synonymous_variant Exon 2 of 4 1 NM_032498.3 ENSP00000360441.3 Q9BQY4

Frequencies

GnomAD3 genomes
AF:
0.000638
AC:
71
AN:
111293
Hom.:
0
Cov.:
19
AF XY:
0.000208
AC XY:
7
AN XY:
33735
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000280
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000165
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00113
Gnomad OTH
AF:
0.000668
GnomAD3 exomes
AF:
0.000544
AC:
98
AN:
180097
Hom.:
2
AF XY:
0.000227
AC XY:
15
AN XY:
66131
show subpopulations
Gnomad AFR exome
AF:
0.000310
Gnomad AMR exome
AF:
0.0000366
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000188
Gnomad NFE exome
AF:
0.00109
Gnomad OTH exome
AF:
0.000670
GnomAD4 exome
AF:
0.00123
AC:
1342
AN:
1093929
Hom.:
8
Cov.:
31
AF XY:
0.000631
AC XY:
227
AN XY:
359601
show subpopulations
Gnomad4 AFR exome
AF:
0.000155
Gnomad4 AMR exome
AF:
0.0000285
Gnomad4 ASJ exome
AF:
0.0000520
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000370
Gnomad4 NFE exome
AF:
0.00150
Gnomad4 OTH exome
AF:
0.00131
GnomAD4 genome
AF:
0.000638
AC:
71
AN:
111336
Hom.:
0
Cov.:
19
AF XY:
0.000207
AC XY:
7
AN XY:
33788
show subpopulations
Gnomad4 AFR
AF:
0.000264
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000281
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000165
Gnomad4 NFE
AF:
0.00113
Gnomad4 OTH
AF:
0.000660
Alfa
AF:
0.000830
Hom.:
5

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Oct 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

RHOXF2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.061
DANN
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs140903249; hg19: chrX-119293123; API