X-102360798-C-T

Variant names:

• chrX-102360798-C-T
• NM_001099686.3:c.1830G>A

Variant summary

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

The NM_001099686.3(NXF2B):​c.1830G>A​(p.Met610Ile) 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: 1.39

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=0.14817005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2B	NM_001099686.3	c.1830G>A	p.Met610Ile	missense_variant	Exon 22 of 23	ENST00000602195.6	NP_001093156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2B	ENST00000602195.6	c.1830G>A	p.Met610Ile	missense_variant	Exon 22 of 23	1	NM_001099686.3	ENSP00000472530.1
ENSG00000284800	ENST00000618302.2	n.*2203G>A		non_coding_transcript_exon_variant	Exon 26 of 27	2		ENSP00000484645.2
ENSG00000284800	ENST00000618302.2	n.*2203G>A		3_prime_UTR_variant	Exon 26 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

Nov 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1830G>A (p.M610I) alteration is located in exon 22 (coding exon 20) of the NXF2B gene. This alteration results from a G to A substitution at nucleotide position 1830, causing the methionine (M) at amino acid position 610 to be replaced by an isoleucine (I). 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	0.18
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.45
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.48	T
Sift4G	Benign	0.20	T;T
Vest4		0.15
MVP		0.11
ClinPred		0.063	T
GERP RS		0.47
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-101615719;