X-102369021-C-G

Variant names:

• chrX-102369021-C-G
• NM_001099686.3:c.535G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001099686.3(NXF2B):​c.535G>C​(p.Asp179His) 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: 0.336

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.066907555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2B	NM_001099686.3	c.535G>C	p.Asp179His	missense_variant	Exon 7 of 23	ENST00000602195.6	NP_001093156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2B	ENST00000602195.6	c.535G>C	p.Asp179His	missense_variant	Exon 7 of 23	1	NM_001099686.3	ENSP00000472530.1
ENSG00000284800	ENST00000618302.2	n.*908G>C		non_coding_transcript_exon_variant	Exon 11 of 27	2		ENSP00000484645.2
ENSG00000284800	ENST00000618302.2	n.*908G>C		3_prime_UTR_variant	Exon 11 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

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.535G>C (p.D179H) alteration is located in exon 7 (coding exon 5) of the NXF2B gene. This alteration results from a G to C substitution at nucleotide position 535, causing the aspartic acid (D) at amino acid position 179 to be replaced by a histidine (H). 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	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.94
FATHMM_MKL	Benign	0.024	N
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.39	T
Sift4G	Uncertain	0.039	D;D
Vest4		0.099
MVP		0.12
ClinPred		0.26	T
GERP RS		0.47
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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-101623942;