X-102321861-C-T

Variant names:

• chrX-102321861-C-T
• rs781974944
• NM_022053.4:c.1271C>T

Variant summary

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

The NM_022053.4(NXF2):​c.1271C>T​(p.Ala424Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A424T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: NXF2 NM_022053.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 2 publications found

Genes affected

NXF2 (HGNC:8072): (nuclear RNA export factor 2) This gene encodes a member of a family of nuclear RNA export proteins. The encoded protein is associated with the nuclear envelope and aids in the export of mRNAs. There is a closely related paralog of this gene located adjacent on chromosome X and on the opposite strand. [provided by RefSeq, Aug 2013]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.1136871).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022053.4. 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
	NXF2	NM_022053.4	MANE Select	c.1271C>T	p.Ala424Val	missense	Exon 16 of 23	NP_071336.1	Q9GZY0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXF2	ENST00000625106.4	TSL:1 MANE Select	c.1271C>T	p.Ala424Val	missense	Exon 16 of 23	ENSP00000485586.2	Q9GZY0
	NXF2	ENST00000604790.2	TSL:1	c.1271C>T	p.Ala424Val	missense	Exon 14 of 21	ENSP00000474598.2	Q9GZY0

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000231 AC: 2

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
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.83	T
PhyloP100		1.5
PrimateAI	Benign	0.47	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.11	B
Vest4		0.11
MutPred		0.49		Loss of disorder (P = 0.0796)
MVP		0.072
ClinPred		0.49	T
GERP RS		0.57
Varity_R		0.035
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs781974944; hg19: chrX-101576775; COSMIC: COSV57649261;