X-120076950-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099685.3(RHOXF2B):​c.418G>C​(p.Ala140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 8)
Exomes 𝑓: 0.000013 ( 0 hom. 7 hem. )
Failed GnomAD Quality Control

Consequence

RHOXF2B
NM_001099685.3 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.52
Variant links:
Genes affected
RHOXF2B (HGNC:33519): (Rhox homeobox family member 2B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in positive regulation of gene expression. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]
RHOXF1-AS1 (HGNC:51582): (RHOXF1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15069875).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHOXF2BNM_001099685.3 linkc.418G>C p.Ala140Pro missense_variant Exon 2 of 4 ENST00000371402.5 NP_001093155.1 P0C7M4
RHOXF1-AS1NR_131238.1 linkn.297+40418C>G intron_variant Intron 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHOXF2BENST00000371402.5 linkc.418G>C p.Ala140Pro missense_variant Exon 2 of 4 1 NM_001099685.3 ENSP00000360455.3 P0C7M4
RHOXF1-AS1ENST00000553843.5 linkn.297+40418C>G intron_variant Intron 1 of 4 2

Frequencies

GnomAD3 genomes
Cov.:
8
GnomAD3 exomes
AF:
0.00000934
AC:
1
AN:
107082
Hom.:
0
AF XY:
0.0000342
AC XY:
1
AN XY:
29212
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000575
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000134
AC:
10
AN:
748345
Hom.:
0
Cov.:
26
AF XY:
0.0000357
AC XY:
7
AN XY:
196307
show subpopulations
Gnomad4 AFR exome
AF:
0.0000588
Gnomad4 AMR exome
AF:
0.0000868
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:
0.0000120
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
8

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 23, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.418G>C (p.A140P) alteration is located in exon 2 (coding exon 2) of the RHOXF2B gene. This alteration results from a G to C substitution at nucleotide position 418, causing the alanine (A) at amino acid position 140 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
0.19
BayesDel_addAF
Benign
-0.089
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
0.0040
DANN
Benign
0.37
DEOGEN2
Benign
0.032
T
FATHMM_MKL
Benign
0.00052
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.15
T
MetaSVM
Benign
-0.30
T
MutationAssessor
Benign
0.46
N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.0
N
REVEL
Uncertain
0.32
Sift
Benign
0.18
T
Sift4G
Benign
0.32
T
Polyphen
0.014
B
Vest4
0.19
MutPred
0.53
Gain of disorder (P = 0.0455);
MVP
0.043
MPC
2.3
ClinPred
0.095
T
GERP RS
-1.9
Varity_R
0.13
gMVP
0.14

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: rs1555996233; hg19: chrX-119210915; API