NM_032498.3:c.282C>T

Variant names:

• chrX-120159217-C-T
• rs140903249
• NM_032498.3:c.282C>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.282C>T​(p.Leu94Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,205,265 control chromosomes in the GnomAD database, including 8 homozygotes. There are 234 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 0.00064 (0 hom., 7 hem., cov: 19)
  • Exomes 𝑓: 0.0012 (8 hom. 227 hem.)
• Consequence: RHOXF2 NM_032498.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant X-120159217-C-T is Benign according to our data. Variant chrX-120159217-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2661316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.86 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 7 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.282C>T	p.Leu94Leu	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.282C>T	p.Leu94Leu	synonymous	Exon 2 of 4	ENSP00000360441.3	Q9BQY4
	RHOXF1	ENST00000703667.1		c.-628-22028G>A		intron	N/A	ENSP00000515423.1	Q8NHV9
	RHOXF1	ENST00000555168.1	TSL:4	n.126-22028G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000638 AC: 71 AN: 111293 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.000668

GnomAD2 exomes AF: 0.000544 AC: 98 AN: 180097 AF XY: 0.000227

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.0000366

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.000670

GnomAD4 exome AF: 0.00123 AC: 1342 AN: 1093929 Hom.: 8 Cov.: 31 AF XY: 0.000631 AC XY: 227 AN XY: 359601

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

African (AFR) AF: 0.000155 AC: 4 AN: 25880

American (AMR) AF: 0.0000285 AC: 1 AN: 35090

Ashkenazi Jewish (ASJ) AF: 0.0000520 AC: 1 AN: 19216

East Asian (EAS) AF: 0.00 AC: 0 AN: 29964

South Asian (SAS) AF: 0.00 AC: 0 AN: 52970

European-Finnish (FIN) AF: 0.000370 AC: 15 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4096

European-Non Finnish (NFE) AF: 0.00150 AC: 1261 AN: 840369

Other (OTH) AF: 0.00131 AC: 60 AN: 45847

⚠️ 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: 0.000638 AC: 71 AN: 111336 Hom.: 0 Cov.: 19 AF XY: 0.000207 AC XY: 7 AN XY: 33788

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

African (AFR) AF: 0.000264 AC: 8 AN: 30265

American (AMR) AF: 0.00 AC: 0 AN: 10723

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3561

South Asian (SAS) AF: 0.00 AC: 0 AN: 2672

European-Finnish (FIN) AF: 0.000165 AC: 1 AN: 6063

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00113 AC: 60 AN: 52995

Other (OTH) AF: 0.000660 AC: 1 AN: 1516

⚠️ 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: 0.000830 Hom.: 5

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	-0.73
CADD	Benign	0.061
DANN	Benign	0.90
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs140903249; hg19: chrX-119293123;