Variant X-120115729-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_139282.3(RHOXF1):c.134T>C(p.Met45Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000828 in 1,207,217 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 1 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.95

Variant links:

Genes affected

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]

RHOXF1 links:

RHOXF1-AS1 (HGNC:51582): (RHOXF1 antisense RNA 1)

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=0.044552356).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOXF1	NM_139282.3 linkuse as main transcript	c.134T>C	p.Met45Thr	missense_variant	1/3	ENST00000217999.3	NP_644811.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-5123A>G		intron_variant, non_coding_transcript_variant
RHOXF1	XM_011531281.3 linkuse as main transcript	c.218T>C	p.Met73Thr	missense_variant	2/4		XP_011529583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.134T>C	p.Met45Thr	missense_variant	1/3	1	NM_139282.3	ENSP00000217999	P1
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-5123A>G		intron_variant, non_coding_transcript_variant		2
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.134T>C	p.Met45Thr	missense_variant	7/9			ENSP00000515423	P1

Frequencies

GnomAD3 genomes

AF:

0.00000903

AC:

AN:

110741

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

32977

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000386

AC:

AN:

181173

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66367

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000220

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:

0.000222

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1096476

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000171

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:

0.00000119

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.00000903

AC:

AN:

110741

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

32977

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

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

Jul 09, 2021

The c.134T>C (p.M45T) alteration is located in exon 1 (coding exon 1) of the RHOXF1 gene. This alteration results from a T to C substitution at nucleotide position 134, causing the methionine (M) at amino acid position 45 to be replaced by a threonine (T). 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

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.46

DANN

Benign

0.30

DEOGEN2

Benign

0.020

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.27

M_CAP

Benign

0.012

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.14

REVEL

Benign

0.097

Sift

Benign

0.29

Sift4G

Benign

0.29

Polyphen

0.084

Vest4

0.12

MutPred

0.24

Gain of glycosylation at M45 (P = 0.0038);

MVP

0.22

MPC

0.25

ClinPred

0.026

GERP RS

-0.87

Varity_R

0.085

gMVP

0.48

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