X-102368550-C-G

Variant names:

• chrX-102368550-C-G
• rs1556390032
• NM_001099686.3:c.705G>C

Variant summary

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

The NM_001099686.3(NXF2B):​c.705G>C​(p.Gln235His) 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: 0.558

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=0.09747803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2B	NM_001099686.3	c.705G>C	p.Gln235His	missense_variant	Exon 9 of 23	ENST00000602195.6	NP_001093156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2B	ENST00000602195.6	c.705G>C	p.Gln235His	missense_variant	Exon 9 of 23	1	NM_001099686.3	ENSP00000472530.1
ENSG00000284800	ENST00000618302.2	n.*1078G>C		non_coding_transcript_exon_variant	Exon 13 of 27	2		ENSP00000484645.2
ENSG00000284800	ENST00000618302.2	n.*1078G>C		3_prime_UTR_variant	Exon 13 of 27	2		ENSP00000484645.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000111 AC: 2 AN: 180518 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66774

Gnomad AFR exome AF: 0.0000794

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.705G>C (p.Q235H) alteration is located in exon 9 (coding exon 7) of the NXF2B gene. This alteration results from a G to C substitution at nucleotide position 705, causing the glutamine (Q) at amino acid position 235 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	0.34
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.28	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.097	T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.077	T;T
Vest4		0.055
MVP		0.33
ClinPred		0.13	T
GERP RS		0.40
gMVP		0.42

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: rs1556390032; hg19: chrX-101623471;