chr6-43524352-CAA-C

Variant names:

• chr6-43524352-CAA-C
• rs368583529
• NM_020750.3:c.3477+117_3477+118delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020750.3(XPO5):​c.3477+117_3477+118delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 1,024,624 control chromosomes in the GnomAD database, including 22 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (20 hom., cov: 26)
  • Exomes 𝑓: 0.058 (2 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO5	NM_020750.3	c.3477+117_3477+118delTT		intron_variant	Intron 31 of 31	ENST00000265351.12	NP_065801.1
POLR1C	NM_001318876.2	c.922+3322_922+3323delAA		intron_variant	Intron 8 of 8		NP_001305805.1
POLR1C	NM_001363658.2	c.922+3322_922+3323delAA		intron_variant	Intron 8 of 9		NP_001350587.1
XPO5	NR_144392.2	n.3789+117_3789+118delTT		intron_variant	Intron 32 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.3477+117_3477+118delTT		intron_variant	Intron 31 of 31	1	NM_020750.3	ENSP00000265351.7

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 1574 AN: 94894 Hom.: 20 Cov.: 26

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.000431

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00513

Gnomad MID AF: 0.0244

Gnomad NFE AF: 0.000781

Gnomad OTH AF: 0.0113

GnomAD4 exome AF: 0.0583 AC: 54157 AN: 929732 Hom.: 2 AF XY: 0.0590 AC XY: 26962 AN XY: 456660

Gnomad4 AFR exome AF: 0.130

Gnomad4 AMR exome AF: 0.0784

Gnomad4 ASJ exome AF: 0.0649

Gnomad4 EAS exome AF: 0.0577

Gnomad4 SAS exome AF: 0.0810

Gnomad4 FIN exome AF: 0.0623

Gnomad4 NFE exome AF: 0.0538

Gnomad4 OTH exome AF: 0.0628

GnomAD4 genome AF: 0.0166 AC: 1578 AN: 94892 Hom.: 20 Cov.: 26 AF XY: 0.0161 AC XY: 720 AN XY: 44752

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.000431

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00513

Gnomad4 NFE AF: 0.000781

Gnomad4 OTH AF: 0.0112

ClinVar

Not reported in ClinVar

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;