rs699937

Positions:

• chr6-43573189-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000265351.12(XPO5):​c.227+291C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,136 control chromosomes in the GnomAD database, including 5,669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5669 hom., cov: 32)
• Consequence: XPO5 ENST00000265351.12 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.249

Genes affected

XPO5 (HGNC:17675): (exportin 5) This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]

POLR1C (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-43573189-G-A is Benign according to our data. Variant chr6-43573189-G-A is described in ClinVar as [Benign]. Clinvar id is 1225218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO5	NM_020750.3	c.227+291C>T		intron_variant		ENST00000265351.12	NP_065801.1
POLR1C	NM_001318876.2	c.945+43918G>A		intron_variant			NP_001305805.1
XPO5	NR_144392.2	n.401+291C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.227+291C>T		intron_variant		1	NM_020750.3	ENSP00000265351	P1
XPO5	ENST00000398799.2	c.*78+209C>T		intron_variant, NMD_transcript_variant		4		ENSP00000381779

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37956 AN: 152020 Hom.: 5665 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.0270

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 37964 AN: 152136 Hom.: 5669 Cov.: 32 AF XY: 0.253 AC XY: 18831 AN XY: 74378

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.242

Alfa AF: 0.302 Hom.: 7283

Bravo AF: 0.240

Asia WGS AF: 0.129 AC: 447 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs699937; hg19: chr6-43540926;