X-102370066-A-C

Variant names:

• chrX-102370066-A-C
• NM_001099686.3:c.130T>G

Variant summary

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

The NM_001099686.3(NXF2B):​c.130T>G​(p.Cys44Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/16 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: NXF2B NM_001099686.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.34

Genes affected

NXF2B (HGNC:23984): (nuclear RNA export factor 2B) 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, Jun 2015]

ENSG00000284800 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07726091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2B	NM_001099686.3	c.130T>G	p.Cys44Gly	missense_variant	Exon 4 of 23	ENST00000602195.6	NP_001093156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2B	ENST00000602195.6	c.130T>G	p.Cys44Gly	missense_variant	Exon 4 of 23	1	NM_001099686.3	ENSP00000472530.1
ENSG00000284800	ENST00000618302.2	n.*503T>G		non_coding_transcript_exon_variant	Exon 8 of 27	2		ENSP00000484645.2
ENSG00000284800	ENST00000618302.2	n.*503T>G		3_prime_UTR_variant	Exon 8 of 27	2		ENSP00000484645.2

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

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.130T>G (p.C44G) alteration is located in exon 4 (coding exon 2) of the NXF2B gene. This alteration results from a T to G substitution at nucleotide position 130, causing the cysteine (C) at amino acid position 44 to be replaced by a glycine (G). 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
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.42
FATHMM_MKL	Benign	0.0035	N
M_CAP	Benign	0.00082	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.40	T;T
Vest4		0.089
MVP		0.043
ClinPred		0.069	T
GERP RS		-5.5
gMVP		0.084

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101624987;