X-102321880-G-C

Position:

• chrX-102321880-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_022053.4(NXF2):​c.1290G>C​(p.Lys430Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/14 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: 2.02

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08837175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF2	NM_022053.4	c.1290G>C	p.Lys430Asn	missense_variant	16/23	ENST00000625106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF2	ENST00000625106.4	c.1290G>C	p.Lys430Asn	missense_variant	16/23	1	NM_022053.4	P1
NXF2	ENST00000604790.2	c.1290G>C	p.Lys430Asn	missense_variant	14/21	1		P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.1290G>C (p.K430N) alteration is located in exon 16 (coding exon 14) of the NXF2 gene. This alteration results from a G to C substitution at nucleotide position 1290, causing the lysine (K) at amino acid position 430 to be replaced by an asparagine (N). 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	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.78
DEOGEN2	Benign	0.016	T;T
FATHMM_MKL	Benign	0.61	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.088	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.49	T
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;B
Vest4		0.038
MutPred		0.45		Loss of methylation at K430 (P = 0.0036);Loss of methylation at K430 (P = 0.0036);
MVP		0.040
ClinPred		0.030	T
GERP RS		0.46
Varity_R		0.059
gMVP		0.079

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: rs1556386392; hg19: chrX-101576794;