X-102360627-C-T

Variant names:

• chrX-102360627-C-T
• rs370144475
• NM_001099686.3:c.1855G>A

Variant summary

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

The NM_001099686.3(NXF2B):​c.1855G>A​(p.Ala619Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 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: 1.29

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=0.065965146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NXF2B	NM_001099686.3	c.1855G>A	p.Ala619Thr	missense_variant	Exon 23 of 23	ENST00000602195.6	NP_001093156.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NXF2B	ENST00000602195.6	c.1855G>A	p.Ala619Thr	missense_variant	Exon 23 of 23	1	NM_001099686.3	ENSP00000472530.1
ENSG00000284800	ENST00000618302.2	n.*2228G>A		non_coding_transcript_exon_variant	Exon 27 of 27	2		ENSP00000484645.2
ENSG00000284800	ENST00000618302.2	n.*2228G>A		3_prime_UTR_variant	Exon 27 of 27	2		ENSP00000484645.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0000973 AC: 14 AN: 143934 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44440

Gnomad AFR exome AF: 0.000175

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000290

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000290

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ESP6500AA AF: 0.000284 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000103 AC: 10

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1855G>A (p.A619T) alteration is located in exon 23 (coding exon 21) of the NXF2B gene. This alteration results from a G to A substitution at nucleotide position 1855, causing the alanine (A) at amino acid position 619 to be replaced by a threonine (T). 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	0.083
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	16
DANN	Uncertain	0.98
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.066	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.041	D;D
Vest4		0.028
MVP		0.13
ClinPred		0.036	T
GERP RS		-2.6
gMVP		0.11

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: rs370144475; hg19: chrX-101615548; COSMIC: COSV57647518; COSMIC: COSV57647518;