chrX-120077048-C-T

Variant names:

• chrX-120077048-C-T
• rs1555996278
• NM_001099685.3:c.320G>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.320G>A​(p.Ser107Asn) 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 0.000023 (0 hom., 1 hem., cov: 14)
  • Exomes 𝑓: 0.0000031 (1 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: RHOXF2B NM_001099685.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.371
• 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=0.131928).

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.320G>A	p.Ser107Asn	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40516C>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.320G>A	p.Ser107Asn	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40516C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000234 AC: 2 AN: 85492 Hom.: 0 Cov.: 14

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000277

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: 0.00000311 AC: 3 AN: 965815 Hom.: 1 Cov.: 30 AF XY: 0.00000362 AC XY: 1 AN XY: 276007

African (AFR) AF: 0.00 AC: 0 AN: 23009

American (AMR) AF: 0.000106 AC: 3 AN: 28393

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16730

East Asian (EAS) AF: 0.00 AC: 0 AN: 21688

South Asian (SAS) AF: 0.00 AC: 0 AN: 38498

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38291

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3676

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 755188

Other (OTH) AF: 0.00 AC: 0 AN: 40342

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000234 AC: 2 AN: 85492 Hom.: 0 Cov.: 14 AF XY: 0.0000498 AC XY: 1 AN XY: 20070

African (AFR) AF: 0.00 AC: 0 AN: 22370

American (AMR) AF: 0.000277 AC: 2 AN: 7223

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2079

East Asian (EAS) AF: 0.00 AC: 0 AN: 2224

South Asian (SAS) AF: 0.00 AC: 0 AN: 1439

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4485

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 43832

Other (OTH) AF: 0.00 AC: 0 AN: 1104

Alfa AF: 0.00 Hom.: 0

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	0.098
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.9
DANN	Benign	0.85
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.37
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.27
Sift	Benign	0.033	D
Sift4G	Benign	0.61	T
Polyphen		0.92	P
Vest4		0.093
MutPred		0.19		Loss of phosphorylation at S107 (P = 0.021)
MVP		0.043
MPC		2.4
ClinPred		0.14	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.12
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: rs1555996278; hg19: chrX-119211013;