Variant X-120112897-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_139282.3(RHOXF1):c.416A>C(p.Asn139Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 112,114 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.17

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:):

RHOXF1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09619373).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHOXF1	NM_139282.3 linkuse as main transcript	c.416A>C	p.Asn139Thr	missense_variant	2/3	ENST00000217999.3	NP_644811.1	Q8NHV9
RHOXF1	XM_011531281.3 linkuse as main transcript	c.500A>C	p.Asn167Thr	missense_variant	3/4		XP_011529583.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-7955T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RHOXF1	ENST00000217999.3 linkuse as main transcript	c.416A>C	p.Asn139Thr	missense_variant	2/3	1	NM_139282.3	ENSP00000217999.1	Q8NHV9
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.416A>C	p.Asn139Thr	missense_variant	8/9			ENSP00000515423.1	Q8NHV9
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-7955T>G		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112114

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34266

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112114

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34266

show subpopulations

Gnomad4 AFR

AF:

0.000162

Gnomad4 AMR

AF:

0.00

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:

0.0000113

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

May 01, 2024

The c.416A>C (p.N139T) alteration is located in exon 2 (coding exon 2) of the RHOXF1 gene. This alteration results from a A to C substitution at nucleotide position 416, causing the asparagine (N) at amino acid position 139 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

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.0030

DANN

Benign

0.44

DEOGEN2

Benign

0.33

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.86

M_CAP

Benign

0.012

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.41

MutationAssessor

Benign

0.13

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.70

REVEL

Benign

0.22

Sift

Benign

0.28

Sift4G

Benign

0.61

Polyphen

0.0030

Vest4

0.19

MVP

0.30

MPC

0.23

ClinPred

0.075

GERP RS

-5.8

Varity_R

0.052

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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