X-120077046-C-T

Variant names:

• chrX-120077046-C-T
• rs2057168368
• NM_001099685.3:c.322G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001099685.3(RHOXF2B):​c.322G>A​(p.Asp108Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 14)
  • Exomes 𝑓: 0.000032 (5 hom. 14 hem.)
  • Failed GnomAD Quality Control
• Consequence: RHOXF2B NM_001099685.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.37
• Publications: 0 publications found

Genes affected

RHOXF2B (HGNC:33519): (Rhox homeobox family member 2B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in positive regulation of gene expression. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

RHOXF1-AS1 (HGNC:51582): (RHOXF1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07324147).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099685.3. 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
	RHOXF2B	NM_001099685.3	MANE Select	c.322G>A	p.Asp108Asn	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40514C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RHOXF2B	ENST00000371402.5	TSL:1 MANE Select	c.322G>A	p.Asp108Asn	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40514C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 85141 Hom.: 0 Cov.: 14

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000321 AC: 31 AN: 966474 Hom.: 5 Cov.: 30 AF XY: 0.0000507 AC XY: 14 AN XY: 276360

African (AFR) AF: 0.00 AC: 0 AN: 23054

American (AMR) AF: 0.00 AC: 0 AN: 28415

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16758

East Asian (EAS) AF: 0.00 AC: 0 AN: 21728

South Asian (SAS) AF: 0.00 AC: 0 AN: 38515

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38297

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3674

European-Non Finnish (NFE) AF: 0.0000397 AC: 30 AN: 755653

Other (OTH) AF: 0.0000248 AC: 1 AN: 40380

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 85141 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 19913

African (AFR) AF: 0.00 AC: 0 AN: 22276

American (AMR) AF: 0.00 AC: 0 AN: 7186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2067

East Asian (EAS) AF: 0.00 AC: 0 AN: 2222

South Asian (SAS) AF: 0.00 AC: 0 AN: 1422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 183

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 43672

Other (OTH) AF: 0.00 AC: 0 AN: 1095

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.055
DANN	Benign	0.92
DEOGEN2	Benign	0.023	T
FATHMM_MKL	Benign	0.00059	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.4
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.31	T
Polyphen		0.90	P
Vest4		0.081
MVP		0.043
MPC		1.9
ClinPred		0.090	T
GERP RS		0.41
Varity_R		0.059
gMVP		0.17
Mutation Taster		=99/1	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: rs2057168368; hg19: chrX-119211011; COSMIC: COSV101003940;