Variant X-120115580-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_139282.3(RHOXF1):c.283G>A(p.Gly95Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,145,252 control chromosomes in the GnomAD database, including 1 homozygotes. There are 10 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 0.000044 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000028 ( 1 hom. 9 hem. )

Consequence

RHOXF1
NM_139282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0820

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06691897).

BS2

High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RHOXF1	NM_139282.3 linkuse as main transcript	c.283G>A	p.Gly95Ser	missense_variant	1/3	ENST00000217999.3	NP_644811.1
RHOXF1-AS1	NR_131238.1 linkuse as main transcript	n.298-5272C>T		intron_variant, non_coding_transcript_variant
RHOXF1	XM_011531281.3 linkuse as main transcript	c.367G>A	p.Gly123Ser	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.283G>A	p.Gly95Ser	missense_variant	1/3	1	NM_139282.3	ENSP00000217999	P1
RHOXF1-AS1	ENST00000553843.5 linkuse as main transcript	n.298-5272C>T		intron_variant, non_coding_transcript_variant		2
RHOXF1	ENST00000703667.1 linkuse as main transcript	c.283G>A	p.Gly95Ser	missense_variant	7/9			ENSP00000515423	P1

Frequencies

GnomAD3 genomes

AF:

0.0000443

AC:

AN:

112953

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

35111

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000938

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000154

AC:

AN:

129757

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

41643

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:

0.0000324

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1032299

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

330509

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:

0.0000358

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000443

AC:

AN:

112953

Hom.:

Cov.:

AF XY:

0.0000285

AC XY:

AN XY:

35111

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000938

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.0000251

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

Feb 15, 2023

The c.283G>A (p.G95S) alteration is located in exon 1 (coding exon 1) of the RHOXF1 gene. This alteration results from a G to A substitution at nucleotide position 283, causing the glycine (G) at amino acid position 95 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.58

CADD

Benign

1.2

DANN

Benign

0.76

DEOGEN2

Benign

0.014

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.42

M_CAP

Benign

0.023

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Benign

0.36

Sift4G

Benign

0.55

Polyphen

0.0010

Vest4

0.083

MutPred

0.22

Gain of phosphorylation at G95 (P = 0.0184);

MVP

0.46

MPC

0.21

ClinPred

0.026

GERP RS

0.80

Varity_R

0.094

gMVP

0.38

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