rs199849270

Positions:

• chrX-101841315-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NR_159737.1(NXF5):​n.508C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000423 in 1,206,403 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 160 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., 12 hem., cov: 20)
  • Exomes 𝑓: 0.00043 (0 hom. 148 hem.)
• Consequence: NXF5 NR_159737.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.91

Genes affected

NXF5 (HGNC:8075): (nuclear RNA export factor 5) This gene is one member of a family of nuclear RNA export factor genes. Most transcript variants are candidates for nonsense-mediated decay (NMD) and may not express proteins in vivo. [provided by RefSeq, Sep 2022]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28517944).
• BS2: High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NXF5	NR_159737.1	n.508C>T		non_coding_transcript_exon_variant	5/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NXF5	ENST00000263032.5	n.697C>T		non_coding_transcript_exon_variant	7/19	1
NXF5	ENST00000537026.6	n.597C>T		non_coding_transcript_exon_variant	6/17	5

Frequencies

GnomAD3 genomes AF: 0.000397 AC: 43 AN: 108436 Hom.: 0 Cov.: 20 AF XY: 0.000390 AC XY: 12 AN XY: 30758

Gnomad AFR AF: 0.000270

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000291

Gnomad SAS AF: 0.00127

Gnomad FIN AF: 0.00106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000478

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000402 AC: 72 AN: 178929 Hom.: 0 AF XY: 0.000403 AC XY: 26 AN XY: 64481

Gnomad AFR exome AF: 0.0000802

Gnomad AMR exome AF: 0.0000739

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000725

Gnomad SAS exome AF: 0.000545

Gnomad FIN exome AF: 0.00102

Gnomad NFE exome AF: 0.000526

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000425 AC: 467 AN: 1097915 Hom.: 0 Cov.: 33 AF XY: 0.000407 AC XY: 148 AN XY: 363325

Gnomad4 AFR exome AF: 0.000379

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000370

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.000428

Gnomad4 OTH exome AF: 0.000391

GnomAD4 genome AF: 0.000396 AC: 43 AN: 108488 Hom.: 0 Cov.: 20 AF XY: 0.000389 AC XY: 12 AN XY: 30822

Gnomad4 AFR AF: 0.000269

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000292

Gnomad4 SAS AF: 0.00127

Gnomad4 FIN AF: 0.00106

Gnomad4 NFE AF: 0.000478

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000648 Hom.: 4

Bravo AF: 0.000321

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.000150 AC: 1

ExAC AF: 0.000453 AC: 55

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Focal segmental glomerulosclerosis Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Sep 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	3.8
DANN	Benign	0.96
DEOGEN2	Benign	0.37	T;.
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.69	T;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Pathogenic	3.2	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Pathogenic	-7.5	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Vest4		0.20
MVP		0.78
MPC		1.8
ClinPred		0.16	T
GERP RS		-0.91
Varity_R		0.23
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs199849270; hg19: chrX-101096287; COSMIC: COSV53790532;