NM_001099685.3:c.247G>A

Variant names:

• chrX-120077121-C-T
• rs782535944
• NM_001099685.3:c.247G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001099685.3(RHOXF2B):​c.247G>A​(p.Ala83Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000643 in 964,456 control chromosomes in the GnomAD database, including 10 homozygotes. There are 13 hemizygotes in GnomAD. 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 0.000047 (1 hom., 0 hem., cov: 14)
  • Exomes 𝑓: 0.000064 (10 hom. 13 hem.)
  • Failed GnomAD Quality Control
• Consequence: RHOXF2B NM_001099685.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.74
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020706534).
• BS2: High Homozygotes in GnomAdExome4 at 10 gene

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.247G>A	p.Ala83Thr	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40589C>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.247G>A	p.Ala83Thr	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40589C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000466 AC: 4 AN: 85769 Hom.: 1 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: 0.000909

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000454

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 17 AN: 152100 AF XY: 0.0000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000500

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000396

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000142

Gnomad OTH exome AF: 0.000260

GnomAD4 exome AF: 0.0000643 AC: 62 AN: 964456 Hom.: 10 Cov.: 30 AF XY: 0.0000472 AC XY: 13 AN XY: 275334

African (AFR) AF: 0.00 AC: 0 AN: 22972

American (AMR) AF: 0.000352 AC: 10 AN: 28413

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16686

East Asian (EAS) AF: 0.0000921 AC: 2 AN: 21711

South Asian (SAS) AF: 0.00 AC: 0 AN: 38489

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38265

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3694

European-Non Finnish (NFE) AF: 0.0000637 AC: 48 AN: 753916

Other (OTH) AF: 0.0000496 AC: 2 AN: 40310

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000466 AC: 4 AN: 85769 Hom.: 1 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 20189

African (AFR) AF: 0.00 AC: 0 AN: 22477

American (AMR) AF: 0.00 AC: 0 AN: 7177

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2077

East Asian (EAS) AF: 0.000909 AC: 2 AN: 2200

South Asian (SAS) AF: 0.00 AC: 0 AN: 1405

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4519

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 180

European-Non Finnish (NFE) AF: 0.0000454 AC: 2 AN: 44091

Other (OTH) AF: 0.00 AC: 0 AN: 1088

Alfa AF: 0.000169 Hom.: 1

ExAC AF: 0.000108 AC: 11

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	0.076
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.022
DANN	Benign	0.95
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.26	N
PhyloP100		-1.7
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.77	N
REVEL	Benign	0.14
Sift	Benign	0.89	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.066
MutPred		0.17		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.043
MPC		1.8
ClinPred		0.0098	T
GERP RS		-0.17
Varity_R		0.026
gMVP		0.070
Mutation Taster		=97/3	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: rs782535944; hg19: chrX-119211086; COSMIC: COSV101003958;