X-102321884-T-C

Variant names:

• chrX-102321884-T-C
• rs1556386393
• NM_022053.4:c.1294T>C

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.1294T>C​(p.Ser432Pro) 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: 2.50

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=0.042355686).
• BP6: Variant X-102321884-T-C is Benign according to our data. Variant chrX-102321884-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2520641.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2	NM_022053.4	c.1294T>C	p.Ser432Pro	missense_variant	Exon 16 of 23	ENST00000625106.4	NP_071336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2	ENST00000625106.4	c.1294T>C	p.Ser432Pro	missense_variant	Exon 16 of 23	1	NM_022053.4	ENSP00000485586.2
NXF2	ENST00000604790.2	c.1294T>C	p.Ser432Pro	missense_variant	Exon 14 of 21	1		ENSP00000474598.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000553 AC: 8 AN: 144624 Hom.: 0 AF XY: 0.0000219 AC XY: 1 AN XY: 45662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00105

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 25, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.76	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.4
DANN	Benign	0.10
DEOGEN2	Benign	0.0066	T;T
FATHMM_MKL	Benign	0.0025	N
LIST_S2	Benign	0.20	.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.042	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.46	T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.048
MutPred		0.39		Loss of phosphorylation at S432 (P = 0.0335);Loss of phosphorylation at S432 (P = 0.0335);
MVP		0.030
ClinPred		0.20	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.11

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: rs1556386393; hg19: chrX-101576798;