chr6-43524352-C-CAA

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020750.3(XPO5):​c.3477+117_3477+118dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,064,304 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 0.00025 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0031 (0 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.3477+118_3477+119insTT		intron_variant	Intron 31 of 31	1	NM_020750.3	ENSP00000265351.7

Frequencies

GnomAD3 genomes AF: 0.000253 AC: 24 AN: 94998 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000746

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000236

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00314 AC: 3039 AN: 969308 Hom.: 0 AF XY: 0.00305 AC XY: 1451 AN XY: 476356

Gnomad4 AFR exome AF: 0.00296

Gnomad4 AMR exome AF: 0.00308

Gnomad4 ASJ exome AF: 0.00437

Gnomad4 EAS exome AF: 0.00316

Gnomad4 SAS exome AF: 0.00389

Gnomad4 FIN exome AF: 0.00136

Gnomad4 NFE exome AF: 0.00314

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.000253 AC: 24 AN: 94996 Hom.: 0 Cov.: 26 AF XY: 0.000268 AC XY: 12 AN XY: 44810

Gnomad4 AFR AF: 0.000745

Gnomad4 AMR AF: 0.000118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000237

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;