X-102360627-C-T

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

Scores

2
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29
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=0.065965146).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NXF2BNM_001099686.3 linkc.1855G>A p.Ala619Thr missense_variant Exon 23 of 23 ENST00000602195.6 NP_001093156.1 Q9GZY0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NXF2BENST00000602195.6 linkc.1855G>A p.Ala619Thr missense_variant Exon 23 of 23 1 NM_001099686.3 ENSP00000472530.1 Q9GZY0
ENSG00000284800ENST00000618302.2 linkn.*2228G>A non_coding_transcript_exon_variant Exon 27 of 27 2 ENSP00000484645.2 A0A2U3TZR1
ENSG00000284800ENST00000618302.2 linkn.*2228G>A 3_prime_UTR_variant Exon 27 of 27 2 ENSP00000484645.2 A0A2U3TZR1

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
show subpopulations
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
LINK: link

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

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

Other links and lift over

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