NM_001099685.3:c.268T>A

Variant names:

• chrX-120077100-A-T
• rs782035552
• NM_001099685.3:c.268T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099685.3(RHOXF2B):​c.268T>A​(p.Trp90Arg) 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: 0.000020 (1 hom. 8 hem.)
  • Failed GnomAD Quality Control
• Consequence: RHOXF2B NM_001099685.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.761
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06464949).

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.268T>A	p.Trp90Arg	missense	Exon 2 of 4	NP_001093155.1	P0C7M4
	RHOXF1-AS1	NR_131238.1		n.297+40568A>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.268T>A	p.Trp90Arg	missense	Exon 2 of 4	ENSP00000360455.3	P0C7M4
	RHOXF1-AS1	ENST00000553843.5	TSL:2	n.297+40568A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000228 AC: 2 AN: 87652 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: 0.0000447

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000327 AC: 5 AN: 153003 AF XY: 0.0000819

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000197 AC: 19 AN: 963783 Hom.: 1 Cov.: 30 AF XY: 0.0000291 AC XY: 8 AN XY: 274873

African (AFR) AF: 0.00 AC: 0 AN: 22924

American (AMR) AF: 0.00 AC: 0 AN: 28370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16656

East Asian (EAS) AF: 0.00 AC: 0 AN: 21679

South Asian (SAS) AF: 0.000208 AC: 8 AN: 38420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38256

Middle Eastern (MID) AF: 0.000271 AC: 1 AN: 3695

European-Non Finnish (NFE) AF: 0.0000119 AC: 9 AN: 753503

Other (OTH) AF: 0.0000248 AC: 1 AN: 40280

GnomAD4 genome AF: 0.0000228 AC: 2 AN: 87652 Hom.: 0 Cov.: 14 AF XY: 0.0000474 AC XY: 1 AN XY: 21110

African (AFR) AF: 0.00 AC: 0 AN: 23058

American (AMR) AF: 0.00 AC: 0 AN: 7407

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2126

East Asian (EAS) AF: 0.00 AC: 0 AN: 2274

South Asian (SAS) AF: 0.00 AC: 0 AN: 1487

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4651

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 188

European-Non Finnish (NFE) AF: 0.0000447 AC: 2 AN: 44783

Other (OTH) AF: 0.00 AC: 0 AN: 1119

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000389 AC: 4

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	0.20
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.32
DANN	Benign	0.42
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.76
PrimateAI	Benign	0.38	T
PROVEAN	Benign	1.0	N
REVEL	Benign	0.14
Sift	Benign	0.19	T
Sift4G	Benign	0.63	T
Polyphen		0.39	B
Vest4		0.072
MutPred		0.31		Gain of methylation at W90 (P = 0.0422)
MVP		0.043
MPC		2.8
ClinPred		0.042	T
GERP RS		-1.6
Varity_R		0.13
gMVP		0.19
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: rs782035552; hg19: chrX-119211065; COSMIC: COSV101003978;