X-102317447-C-T

Variant names:

• chrX-102317447-C-T
• NM_022053.4:c.302C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_022053.4(NXF2):​c.302C>T​(p.Thr101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: NXF2 NM_022053.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.242

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057052612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2	NM_022053.4	c.302C>T	p.Thr101Met	missense_variant	Exon 5 of 23	ENST00000625106.4	NP_071336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2	ENST00000625106.4	c.302C>T	p.Thr101Met	missense_variant	Exon 5 of 23	1	NM_022053.4	ENSP00000485586.2
NXF2	ENST00000604790.2	c.302C>T	p.Thr101Met	missense_variant	Exon 3 of 21	1		ENSP00000474598.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 30, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302C>T (p.T101M) alteration is located in exon 5 (coding exon 3) of the NXF2 gene. This alteration results from a C to T substitution at nucleotide position 302, causing the threonine (T) at amino acid position 101 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.7
DANN	Benign	0.66
DEOGEN2	Benign	0.0078	T;T
FATHMM_MKL	Benign	0.00032	N
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.73	T;T
Polyphen		0.011	B;B
Vest4		0.075
MutPred		0.34		Loss of glycosylation at T101 (P = 0.0153);Loss of glycosylation at T101 (P = 0.0153);
MVP		0.040
ClinPred		0.031	T
GERP RS		-2.2
Varity_R		0.018
gMVP		0.19

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101572404; COSMIC: COSV57647435;