6-43524352-CAAAAAAAAA-CAAAAAA

Variant names:

• chr6-43524352-CAAA-C
• rs368583529
• NM_020750.3:c.3477+116_3477+118delTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_020750.3(XPO5):​c.3477+116_3477+118delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00668 in 1,053,426 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0073 (0 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00733 (7029/958434) while in subpopulation AFR AF= 0.0164 (345/20992). AF 95% confidence interval is 0.015. There are 0 homozygotes in gnomad4_exome. There are 3523 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO5	NM_020750.3	c.3477+116_3477+118delTTT		intron_variant	Intron 31 of 31	ENST00000265351.12	NP_065801.1
POLR1C	NM_001318876.2	c.922+3321_922+3323delAAA		intron_variant	Intron 8 of 8		NP_001305805.1
POLR1C	NM_001363658.2	c.922+3321_922+3323delAAA		intron_variant	Intron 8 of 9		NP_001350587.1
XPO5	NR_144392.2	n.3789+116_3789+118delTTT		intron_variant	Intron 32 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.3477+116_3477+118delTTT		intron_variant	Intron 31 of 31	1	NM_020750.3	ENSP00000265351.7

Frequencies

GnomAD3 genomes AF: 0.000126 AC: 12 AN: 94994 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000637

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00733 AC: 7029 AN: 958434 Hom.: 0 AF XY: 0.00748 AC XY: 3523 AN XY: 470878

Gnomad4 AFR exome AF: 0.0164

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.00836

Gnomad4 EAS exome AF: 0.00684

Gnomad4 SAS exome AF: 0.0124

Gnomad4 FIN exome AF: 0.00762

Gnomad4 NFE exome AF: 0.00662

Gnomad4 OTH exome AF: 0.00811

GnomAD4 genome AF: 0.000137 AC: 13 AN: 94992 Hom.: 0 Cov.: 26 AF XY: 0.000112 AC XY: 5 AN XY: 44804

Gnomad4 AFR AF: 0.000102

Gnomad4 AMR AF: 0.000118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000346

Gnomad4 FIN AF: 0.000637

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00

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;