Variant X-120077124-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000371402.5(RHOXF2B):c.244G>A(p.Gly82Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 962,858 control chromosomes in the GnomAD database, including 22 homozygotes. There are 25 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000082 ( 2 hom., 1 hem., cov: 14)

Exomes 𝑓: 0.00011 ( 22 hom. 25 hem. )

Failed GnomAD Quality Control

Consequence

RHOXF2B
ENST00000371402.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.235

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049141943).

BP6

Variant X-120077124-C-T is Benign according to our data. Variant chrX-120077124-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2661314.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF2B	NM_001099685.3 linkuse as main transcript	c.244G>A	p.Gly82Ser	missense_variant	2/4	ENST00000371402.5	NP_001093155.1	P0C7M4
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.297+40592C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHOXF2B	ENST00000371402.5 linkuse as main transcript	c.244G>A	p.Gly82Ser	missense_variant	2/4	1	NM_001099685.3	ENSP00000360455.3		P0C7M4
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.297+40592C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

85099

Hom.:

Cov.:

AF XY:

0.0000502

AC XY:

AN XY:

19913

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00230

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000457

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000316

AC:

AN:

151857

Hom.:

AF XY:

0.000144

AC XY:

AN XY:

48605

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000428

Gnomad OTH exome

AF:

0.000262

GnomAD4 exome

AF:

0.000107

AC:

103

AN:

962858

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

275030

show subpopulations

Gnomad4 AFR exome

AF:

0.0000436

Gnomad4 AMR exome

AF:

0.0000704

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00336

Gnomad4 SAS exome

AF:

0.0000260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000253

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000823

AC:

AN:

85099

Hom.:

Cov.:

AF XY:

0.0000502

AC XY:

AN XY:

19913

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00230

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000457

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000265

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

RHOXF2B: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.32

DANN

Benign

0.95

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.33

M_CAP

Benign

0.0082

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.76

REVEL

Benign

0.14

Sift

Benign

0.081

Sift4G

Benign

0.41

Polyphen

0.021

Vest4

0.090

MutPred

0.34

Gain of phosphorylation at G82 (P = 0.0123);

MVP

0.14

MPC

1.8

ClinPred

0.0083

Varity_R

0.097

gMVP

0.082

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