6-43524352-CA-C

Position:

• chr6-43524352-CA-C

Variant summary

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

The NM_020750.3(XPO5):​c.3477+118del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 94,942 control chromosomes in the GnomAD database, including 2,282 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (2282 hom., cov: 26)
  • Exomes 𝑓: 0.32 (178 hom.)
  • Failed GnomAD Quality Control
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: 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-CA-C is Benign according to our data. Variant chr6-43524352-CA-C is described in ClinVar as [Benign]. Clinvar id is 1273091.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.236 AC: 22370 AN: 94946 Hom.: 2278 Cov.: 26

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.0558

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.232

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.317 AC: 300465 AN: 946980 Hom.: 178 AF XY: 0.318 AC XY: 147907 AN XY: 464926

Gnomad4 AFR exome AF: 0.355

Gnomad4 AMR exome AF: 0.317

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.319

Gnomad4 SAS exome AF: 0.317

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.320

GnomAD4 genome AF: 0.236 AC: 22388 AN: 94942 Hom.: 2282 Cov.: 26 AF XY: 0.239 AC XY: 10686 AN XY: 44788

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0949

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.160

Gnomad4 OTH AF: 0.232

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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;