X-109535940-A-T

Position:

• chrX-109535940-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000218004.5(NXT2):​c.58A>T​(p.Ser20Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NXT2 ENST00000218004.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.383

Genes affected

NXT2 (HGNC:18151): (nuclear transport factor 2 like export factor 2) The protein encoded by this gene contains a nuclear transport factor 2 (NTF2) domain, which plays an important role in the trafficking of macromolecules, ions, and small molecules between the cytoplasm and nucleus. This protein may also have a role in mRNA nuclear export. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09733999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXT2	NM_018698.5	c.58A>T	p.Ser20Cys	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXT2	ENST00000218004.5	c.58A>T	p.Ser20Cys	missense_variant	1/5	1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.58A>T (p.S20C) alteration is located in exon 1 (coding exon 1) of the NXT2 gene. This alteration results from a A to T substitution at nucleotide position 58, causing the serine (S) at amino acid position 20 to be replaced by a cysteine (C). 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
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.018
DANN	Benign	0.93
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.088	T
Polyphen		0.98	D
Vest4		0.17
MutPred		0.22		Loss of phosphorylation at S20 (P = 0.0171);
MVP		0.093
MPC		0.16
ClinPred		0.40	T
GERP RS		-3.3
gMVP		0.11

Splicing

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-108779169;