dbSNP rs1555996357: RHOXF2B:p.Glu51Lys (chrX-120077217-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099685.3(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. 15/21 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
NM_001099685.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0930

Publications

0 publications found

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:51582): (RHOXF1 antisense RNA 1)

RHOXF1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099685.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOXF2B	NM_001099685.3	MANE Select	c.151G>A	p.Glu51Lys	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40685C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOXF2B	ENST00000371402.5	TSL:1 MANE Select	c.151G>A	p.Glu51Lys	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40685C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000957

AC:

AN:

104547

AF XY:

0.00

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 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

African (AFR)

AF:

0.00

AC:

AN:

21542

American (AMR)

AF:

0.00

AC:

AN:

27352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16111

East Asian (EAS)

AF:

0.00

AC:

AN:

20986

South Asian (SAS)

AF:

0.00

AC:

AN:

36662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37773

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3250

European-Non Finnish (NFE)

AF:

0.00000143

AC:

AN:

698460

Other (OTH)

AF:

0.00

AC:

AN:

38009

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.2

(source)

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

PhyloP100

0.093

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

PromoterAI

0.052

Neutral

(source)

Varity_R

0.12

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over