NM_001099686.3:c.658A>T

Variant summary

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

The NM_001099686.3(NXF2B):​c.658A>T​(p.Thr220Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/16 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

Scores

11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.287
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.060505033).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NXF2BNM_001099686.3 linkc.658A>T p.Thr220Ser missense_variant Exon 9 of 23 ENST00000602195.6 NP_001093156.1 Q9GZY0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NXF2BENST00000602195.6 linkc.658A>T p.Thr220Ser missense_variant Exon 9 of 23 1 NM_001099686.3 ENSP00000472530.1 Q9GZY0
ENSG00000284800ENST00000618302.2 linkn.*1031A>T non_coding_transcript_exon_variant Exon 13 of 27 2 ENSP00000484645.2 A0A2U3TZR1
ENSG00000284800ENST00000618302.2 linkn.*1031A>T 3_prime_UTR_variant Exon 13 of 27 2 ENSP00000484645.2 A0A2U3TZR1

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD3 exomes
AF:
0.0000109
AC:
2
AN:
182659
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67425
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000246
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
0
GnomAD4 genome
Cov.:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.658A>T (p.T220S) alteration is located in exon 9 (coding exon 7) of the NXF2B gene. This alteration results from a A to T substitution at nucleotide position 658, causing the threonine (T) at amino acid position 220 to be replaced by a serine (S). 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
-0.23
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
5.8
DANN
Benign
0.76
FATHMM_MKL
Benign
0.071
N
M_CAP
Benign
0.0039
T
MetaRNN
Benign
0.061
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.36
T
Sift4G
Benign
0.42
T;T
Vest4
0.093
MVP
0.12
ClinPred
0.047
T
GERP RS
-1.9
gMVP
0.24

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782651175; hg19: chrX-101623518; API