6-43524352-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020750.3(XPO5):c.3477+118_3477+119insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,062,066 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (10 hom., cov: 26)
  • Exomes 𝑓: 0.072 (1 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.387

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 -10 ACMG points.

• BP6: Variant 6-43524352-C-CA is Benign according to our data. Variant chr6-43524352-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1317562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO5	NM_020750.3	c.3477+118_3477+119insT		intron_variant		ENST00000265351.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO5	ENST00000265351.12	c.3477+118_3477+119insT		intron_variant		1	NM_020750.3	P1

Frequencies

GnomAD3 genomes AF: 0.0145 AC: 1379 AN: 94934 Hom.: 10 Cov.: 26

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.00429

Gnomad AMR AF: 0.00885

Gnomad ASJ AF: 0.0479

Gnomad EAS AF: 0.00613

Gnomad SAS AF: 0.0206

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0976

Gnomad NFE AF: 0.00561

Gnomad OTH AF: 0.0145

GnomAD4 exome AF: 0.0720 AC: 69653 AN: 967134 Hom.: 1 AF XY: 0.0714 AC XY: 33916 AN XY: 475198

Gnomad4 AFR exome AF: 0.0522

Gnomad4 AMR exome AF: 0.0615

Gnomad4 ASJ exome AF: 0.0825

Gnomad4 EAS exome AF: 0.0655

Gnomad4 SAS exome AF: 0.0690

Gnomad4 FIN exome AF: 0.0472

Gnomad4 NFE exome AF: 0.0742

Gnomad4 OTH exome AF: 0.0696

GnomAD4 genome AF: 0.0145 AC: 1379 AN: 94932 Hom.: 10 Cov.: 26 AF XY: 0.0146 AC XY: 655 AN XY: 44772

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.00886

Gnomad4 ASJ AF: 0.0479

Gnomad4 EAS AF: 0.00615

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.0104

Gnomad4 NFE AF: 0.00563

Gnomad4 OTH AF: 0.0144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs368583529; hg19: chr6-43492090;