rs782713247

Variant names:

• chrX-120159425-C-A
• rs782713247
• NM_032498.3:c.490C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-120159425-C-A
• chrX-120159425-C-G
• chrX-120159425-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_032498.3(RHOXF2):​c.490C>A​(p.Arg164Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000639 in 1,094,811 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. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 19)
  • Exomes 𝑓: 0.0000064 (0 hom. 2 hem.)
• Consequence: RHOXF2 NM_032498.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00002513
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 0 publications found

Genes affected

RHOXF2 (HGNC:30011): (Rhox homeobox family member 2) This gene, which encodes a transcriptional repressor, is one of two paralogous X-linked homeobox-containing genes and is highly expressed in a variety of cancers. In addition, the encoded protein associates with the cell membrane and with microtubules, and is concentrated at the leading edge of migratory cells. [provided by RefSeq, Dec 2015]

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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.23 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032498.3. 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
	RHOXF2	NM_032498.3	MANE Select	c.490C>A	p.Arg164Arg	splice_region synonymous	Exon 2 of 4	NP_115887.1	Q9BQY4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOXF2	ENST00000371388.5	TSL:1 MANE Select	c.490C>A	p.Arg164Arg	splice_region synonymous	Exon 2 of 4	ENSP00000360441.3	Q9BQY4
	RHOXF1	ENST00000703667.1		c.-628-22236G>T		intron	N/A	ENSP00000515423.1	Q8NHV9
	RHOXF1	ENST00000555168.1	TSL:4	n.126-22236G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 19

GnomAD2 exomes AF: 0.0000173 AC: 3 AN: 173476 AF XY: 0.0000163

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: 0.000196

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000639 AC: 7 AN: 1094811 Hom.: 0 Cov.: 32 AF XY: 0.00000555 AC XY: 2 AN XY: 360553

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000760 AC: 2 AN: 26324

American (AMR) AF: 0.00 AC: 0 AN: 35081

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19354

East Asian (EAS) AF: 0.00 AC: 0 AN: 30105

South Asian (SAS) AF: 0.00 AC: 0 AN: 53671

European-Finnish (FIN) AF: 0.0000497 AC: 2 AN: 40247

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3845

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840253

Other (OTH) AF: 0.0000218 AC: 1 AN: 45931

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00335540), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 19

Alfa AF: 0.000264 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.51
DANN	Benign	0.52
PhyloP100		-1.2
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.072
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

Other links and lift over

dbSNP: rs782713247; hg19: chrX-119293331;