6-43523597-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_020750.3(XPO5):c.*271A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 659,036 control chromosomes in the GnomAD database, including 1,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (184 hom., cov: 32)
  • Exomes 𝑓: 0.053 (875 hom.)
• Consequence: XPO5 NM_020750.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0390

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:20194): (RNA polymerase I and III subunit C) The protein encoded by this gene is a subunit of both RNA polymerase I and RNA polymerase III complexes. The encoded protein is part of the Pol core element. Mutations in this gene have been associated with Treacher Collins syndrome (TCS) and hypomyelinating leukodystrophy 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 6-43523597-T-C is Benign according to our data. Variant chr6-43523597-T-C is described in ClinVar as [Benign]. Clinvar id is 1227838.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO5	NM_020750.3	c.*271A>G		3_prime_UTR_variant	32/32	ENST00000265351.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO5	ENST00000265351.12	c.*271A>G		3_prime_UTR_variant	32/32	1	NM_020750.3	P1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6629 AN: 152210 Hom.: 184 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0543

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0655

Gnomad OTH AF: 0.0455

GnomAD4 exome AF: 0.0529 AC: 26819 AN: 506708 Hom.: 875 Cov.: 5 AF XY: 0.0528 AC XY: 14680 AN XY: 278282

Gnomad4 AFR exome AF: 0.0108

Gnomad4 AMR exome AF: 0.0369

Gnomad4 ASJ exome AF: 0.0368

Gnomad4 EAS exome AF: 0.000864

Gnomad4 SAS exome AF: 0.0394

Gnomad4 FIN exome AF: 0.0608

Gnomad4 NFE exome AF: 0.0655

Gnomad4 OTH exome AF: 0.0497

GnomAD4 genome AF: 0.0435 AC: 6627 AN: 152328 Hom.: 184 Cov.: 32 AF XY: 0.0427 AC XY: 3182 AN XY: 74504

Gnomad4 AFR AF: 0.0112

Gnomad4 AMR AF: 0.0430

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0445

Gnomad4 FIN AF: 0.0543

Gnomad4 NFE AF: 0.0655

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0598 Hom.: 61

Bravo AF: 0.0398

Asia WGS AF: 0.0330 AC: 116 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 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	11
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs55671916; hg19: chr6-43491335;