X-102317438-G-A

Position:

• chrX-102317438-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_022053.4(NXF2):​c.293G>A​(p.Arg98His) 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 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: -0.0990

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.057541758).
• BP6: Variant X-102317438-G-A is Benign according to our data. Variant chrX-102317438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3203479.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF2	NM_022053.4	c.293G>A	p.Arg98His	missense_variant	5/23	ENST00000625106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF2	ENST00000625106.4	c.293G>A	p.Arg98His	missense_variant	5/23	1	NM_022053.4	P1
NXF2	ENST00000604790.2	c.293G>A	p.Arg98His	missense_variant	3/21	1		P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ExAC AF: 0.0000358 AC: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.038
DANN	Benign	0.51
DEOGEN2	Benign	0.0077	T;T
FATHMM_MKL	Benign	0.00069	N
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.39	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;B
Vest4		0.063
MutPred		0.37		Loss of sheet (P = 0.0181);Loss of sheet (P = 0.0181);
MVP		0.055
ClinPred		0.063	T
GERP RS		-2.6
Varity_R		0.035
gMVP		0.12

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: rs782235868; hg19: chrX-101572395; COSMIC: COSV57648819;