X-102317416-T-C

Variant names:

• chrX-102317416-T-C
• rs782256203
• NM_022053.4:c.271T>C

Variant summary

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

The NM_022053.4(NXF2):​c.271T>C​(p.Trp91Arg) 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: -1.10

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=0.059096336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2	NM_022053.4	c.271T>C	p.Trp91Arg	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.271T>C	p.Trp91Arg	missense_variant	Exon 5 of 23	1	NM_022053.4	ENSP00000485586.2
NXF2	ENST00000604790.2	c.271T>C	p.Trp91Arg	missense_variant	Exon 3 of 21	1		ENSP00000474598.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000354 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271T>C (p.W91R) alteration is located in exon 5 (coding exon 3) of the NXF2 gene. This alteration results from a T to C substitution at nucleotide position 271, causing the tryptophan (W) at amino acid position 91 to be replaced by an arginine (R). 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	-0.64	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.41
DEOGEN2	Benign	0.073	T;T
FATHMM_MKL	Benign	0.0042	N
LIST_S2	Benign	0.098	.;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.42	T
Sift4G	Benign	0.37	T;T
Polyphen		0.022	B;B
Vest4		0.10
MutPred		0.34		Loss of ubiquitination at K90 (P = 0.0502);Loss of ubiquitination at K90 (P = 0.0502);
MVP		0.030
ClinPred		0.033	T
GERP RS		-3.3
Varity_R		0.057
gMVP		0.16

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

LitVar

Other links and lift over

dbSNP: rs782256203; hg19: chrX-101572373;