rs28574753

Variant names:

• chr16-28098439-G-A
• rs28574753
• NM_015171.4:c.*99C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015171.4(XPO6):​c.*99C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00496 in 1,050,768 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.016 (35 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (39 hom.)
• Consequence: XPO6 NM_015171.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 publications found

Genes affected

XPO6 (HGNC:19733): (exportin 6) The protein encoded by this gene is a member of the importin-beta family. Members of this family are regulated by the GTPase Ran to mediate transport of cargo across the nuclear envelope. This protein has been shown to mediate nuclear export of profilin-actin complexes. A pseudogene of this gene is located on the long arm of chromosome 14. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Aug 2012]

ENSG00000310204 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0158 (2400/152316) while in subpopulation AFR AF = 0.0467 (1943/41572). AF 95% confidence interval is 0.045. There are 35 homozygotes in GnomAd4. There are 1208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2400 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO6	NM_015171.4	c.*99C>T		3_prime_UTR_variant	Exon 24 of 24	ENST00000304658.10	NP_055986.1
XPO6	NM_001270940.2	c.*99C>T		3_prime_UTR_variant	Exon 25 of 25		NP_001257869.1
LOC124903669	XR_007065032.1	n.89+861G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO6	ENST00000304658.10	c.*99C>T		3_prime_UTR_variant	Exon 24 of 24	1	NM_015171.4	ENSP00000302790.4
XPO6	ENST00000565698.5	c.*99C>T		3_prime_UTR_variant	Exon 25 of 25	2		ENSP00000457341.1
XPO6	ENST00000568065.5	c.*99C>T		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000456422.1
ENSG00000310204	ENST00000848143.1	n.148+861G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0157 AC: 2396 AN: 152198 Hom.: 35 Cov.: 32

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00313 AC: 2812 AN: 898452 Hom.: 39 Cov.: 12 AF XY: 0.00299 AC XY: 1362 AN XY: 456084

African (AFR) AF: 0.0463 AC: 1018 AN: 22002

American (AMR) AF: 0.00666 AC: 227 AN: 34090

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 523 AN: 17882

East Asian (EAS) AF: 0.00 AC: 0 AN: 34990

South Asian (SAS) AF: 0.000400 AC: 25 AN: 62546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39068

Middle Eastern (MID) AF: 0.0107 AC: 33 AN: 3070

European-Non Finnish (NFE) AF: 0.00102 AC: 657 AN: 643702

Other (OTH) AF: 0.00800 AC: 329 AN: 41102

GnomAD4 genome AF: 0.0158 AC: 2400 AN: 152316 Hom.: 35 Cov.: 32 AF XY: 0.0162 AC XY: 1208 AN XY: 74474

African (AFR) AF: 0.0467 AC: 1943 AN: 41572

American (AMR) AF: 0.0141 AC: 216 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 93 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00159 AC: 108 AN: 68030

Other (OTH) AF: 0.0152 AC: 32 AN: 2112

Alfa AF: 0.00755 Hom.: 7

Bravo AF: 0.0172

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.77
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28574753; hg19: chr16-28109760;