X-102321861-C-T

Position:

• chrX-102321861-C-T

Variant summary

Our verdict is Likely benign. Variant got -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. 9/14 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

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=0.1136871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF2	NM_022053.4	c.1271C>T	p.Ala424Val	missense_variant	16/23	ENST00000625106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF2	ENST00000625106.4	c.1271C>T	p.Ala424Val	missense_variant	16/23	1	NM_022053.4	P1
NXF2	ENST00000604790.2	c.1271C>T	p.Ala424Val	missense_variant	14/21	1		P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000231 AC: 2

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

Feb 22, 2023

The c.1271C>T (p.A424V) alteration is located in exon 16 (coding exon 14) of the NXF2 gene. This alteration results from a C to T substitution at nucleotide position 1271, causing the alanine (A) at amino acid position 424 to be replaced by a valine (V). 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	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;T
FATHMM_MKL	Benign	0.76	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.83	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.47	T
Sift4G	Uncertain	0.0060	D;D
Polyphen		0.11	B;B
Vest4		0.11
MutPred		0.49		Loss of disorder (P = 0.0796);Loss of disorder (P = 0.0796);
MVP		0.072
ClinPred		0.49	T
GERP RS		0.57
Varity_R		0.035
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs781974944; hg19: chrX-101576775; COSMIC: COSV57649261;