Variant chrX-120077217-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000371402.5(RHOXF2B):c.151G>A(p.Glu51Lys) 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: 6)

Exomes 𝑓: 0.0000011 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2B
ENST00000371402.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0930

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]

RHOXF2B links:

RHOXF1-AS1 (HGNC:):

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057896942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2B	NM_001099685.3 linkuse as main transcript	c.151G>A	p.Glu51Lys	missense_variant	2/4	ENST00000371402.5	NP_001093155.1	P0C7M4
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.297+40685C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2B	ENST00000371402.5 linkuse as main transcript	c.151G>A	p.Glu51Lys	missense_variant	2/4	1	NM_001099685.3	ENSP00000360455.3		P0C7M4
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.297+40685C>T		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000957

AC:

AN:

104547

Hom.:

AF XY:

0.00

AC XY:

AN XY:

28155

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:

0.0000226

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000111

AC:

AN:

900145

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

250853

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:

0.00000143

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 19, 2024

The c.151G>A (p.E51K) alteration is located in exon 2 (coding exon 2) of the RHOXF2B gene. This alteration results from a G to A substitution at nucleotide position 151, causing the glutamic acid (E) at amino acid position 51 to be replaced by a lysine (K). 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

0.079

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.61

M_CAP

Benign

0.0059

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.90

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Benign

0.031

Sift4G

Benign

0.065

Polyphen

0.12

Vest4

0.15

MutPred

0.31

Gain of ubiquitination at E51 (P = 0.0025);

MVP

0.043

MPC

2.1

ClinPred

0.048

GERP RS

-1.7

Varity_R

0.12

gMVP

0.052

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