X-120159346-C-T

Variant names:

• chrX-120159346-C-T
• rs142963365
• NM_032498.3:c.411C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032498.3(RHOXF2):​c.411C>T​(p.Asn137Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00134 in 1,207,155 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., 4 hem., cov: 19)
  • Exomes 𝑓: 0.0014 (0 hom. 20 hem.)
• Consequence: RHOXF2 NM_032498.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04
• Publications: 4 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant X-120159346-C-T is Benign according to our data. Variant chrX-120159346-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661317.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.04 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 4 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.411C>T	p.Asn137Asn	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.411C>T	p.Asn137Asn	synonymous	Exon 2 of 4	ENSP00000360441.3	Q9BQY4
	RHOXF1	ENST00000703667.1		c.-628-22157G>A		intron	N/A	ENSP00000515423.1	Q8NHV9
	RHOXF1	ENST00000555168.1	TSL:4	n.126-22157G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000779 AC: 88 AN: 112933 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00130

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: 0.00117

Gnomad OTH AF: 0.00264

GnomAD2 exomes AF: 0.000898 AC: 159 AN: 177066 AF XY: 0.0000470

Gnomad AFR exome AF: 0.000473

Gnomad AMR exome AF: 0.000919

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.00136

GnomAD4 exome AF: 0.00140 AC: 1534 AN: 1094172 Hom.: 0 Cov.: 31 AF XY: 0.0000554 AC XY: 20 AN XY: 360876

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

African (AFR) AF: 0.000304 AC: 8 AN: 26352

American (AMR) AF: 0.00114 AC: 40 AN: 35074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.0000663 AC: 2 AN: 30147

South Asian (SAS) AF: 0.00 AC: 0 AN: 53929

European-Finnish (FIN) AF: 0.0000495 AC: 2 AN: 40426

Middle Eastern (MID) AF: 0.000501 AC: 2 AN: 3996

European-Non Finnish (NFE) AF: 0.00170 AC: 1428 AN: 838984

Other (OTH) AF: 0.00113 AC: 52 AN: 45899

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000761 AC: 86 AN: 112983 Hom.: 0 Cov.: 19 AF XY: 0.000113 AC XY: 4 AN XY: 35261

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

African (AFR) AF: 0.000256 AC: 8 AN: 31244

American (AMR) AF: 0.00120 AC: 13 AN: 10811

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2660

East Asian (EAS) AF: 0.00 AC: 0 AN: 3627

South Asian (SAS) AF: 0.00 AC: 0 AN: 2858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00115 AC: 61 AN: 53078

Other (OTH) AF: 0.00261 AC: 4 AN: 1535

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00138 Hom.: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.75
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142963365; hg19: chrX-119293252; COSMIC: COSV65047671;