chrX-102321892-G-A

Position:

• chrX-102321892-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PVS1_Moderate BP6_Moderate

The NM_022053.4(NXF2):​c.1301+1G>A variant causes a splice donor change. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: NXF2 NM_022053.4 splice_donor
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.58

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 Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.056884635 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BP6: Variant X-102321892-G-A is Benign according to our data. Variant chrX-102321892-G-A is described in ClinVar as [Benign]. Clinvar id is 770021.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-102321892-G-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF2	NM_022053.4	c.1301+1G>A		splice_donor_variant		ENST00000625106.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF2	ENST00000625106.4	c.1301+1G>A		splice_donor_variant		1	NM_022053.4	P1
NXF2	ENST00000604790.2	c.1301+1G>A		splice_donor_variant		1		P1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0457 AC: 6290 AN: 137549 Hom.: 1850 AF XY: 0.0496 AC XY: 2136 AN XY: 43041

Gnomad AFR exome AF: 0.0143

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.00626

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.0804

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.0141

Gnomad OTH exome AF: 0.0467

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.101 Hom.: 416

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.98
FATHMM_MKL	Uncertain	0.90	D
MutationTaster	Benign	1.0	D;D;D;D;D
GERP RS		2.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.99		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60955190; hg19: chrX-101576806; COSMIC: COSV99042627;