NM_022053.4:c.1294T>C

Variant names:

• chrX-102321884-T-C
• rs1556386393
• NM_022053.4:c.1294T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_022053.4(NXF2):​c.1294T>C​(p.Ser432Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: NXF2 NM_022053.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.50
• Publications: 0 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.042355686).
• BP6: Variant X-102321884-T-C is Benign according to our data. Variant chrX-102321884-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2520641.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1294T>C	p.Ser432Pro	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.1294T>C	p.Ser432Pro	missense	Exon 16 of 23	ENSP00000485586.2	Q9GZY0
	NXF2	ENST00000604790.2	TSL:1	c.1294T>C	p.Ser432Pro	missense	Exon 14 of 21	ENSP00000474598.2	Q9GZY0

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.0000553 AC: 8 AN: 144624 AF XY: 0.0000219

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00105

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	-0.76	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.10
DEOGEN2	Benign	0.0066	T
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.5
PrimateAI	Benign	0.46	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.048
MutPred		0.39		Loss of phosphorylation at S432 (P = 0.0335)
MVP		0.030
ClinPred		0.20	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.11

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: rs1556386393; hg19: chrX-101576798;