rs28574753

Positions:

• chr16-28098439-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124903669 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2400 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO6	ENST00000304658	c.*99C>T		3_prime_UTR_variant	24/24	1	NM_015171.4	ENSP00000302790.4
XPO6	ENST00000565698	c.*99C>T		3_prime_UTR_variant	25/25	2		ENSP00000457341.1
XPO6	ENST00000568065	c.*99C>T		3_prime_UTR_variant	3/3	5		ENSP00000456422.1

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

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.00666

Gnomad4 ASJ exome AF: 0.0292

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000400

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00102

Gnomad4 OTH exome AF: 0.00800

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

Gnomad4 AFR AF: 0.0467

Gnomad4 AMR AF: 0.0141

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00706 Hom.: 4

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs28574753; hg19: chr16-28109760;