chr6-43524352-CAAAAAAA-C

Variant names:

• chr6-43524352-CAAAAAAA-C
• rs368583529
• NM_020750.3:c.3477+112_3477+118delTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020750.3(XPO5):​c.3477+112_3477+118delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 95,022 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 0.000021 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPO5	NM_020750.3	c.3477+112_3477+118delTTTTTTT		intron_variant	Intron 31 of 31	ENST00000265351.12	NP_065801.1
POLR1C	NM_001318876.2	c.922+3317_922+3323delAAAAAAA		intron_variant	Intron 8 of 8		NP_001305805.1
POLR1C	NM_001363658.2	c.922+3317_922+3323delAAAAAAA		intron_variant	Intron 8 of 9		NP_001350587.1
XPO5	NR_144392.2	n.3789+112_3789+118delTTTTTTT		intron_variant	Intron 32 of 32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.3477+112_3477+118delTTTTTTT		intron_variant	Intron 31 of 31	1	NM_020750.3	ENSP00000265351.7

Frequencies

GnomAD3 genomes AF: 0.0000210 AC: 2 AN: 95022 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000473

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000205 AC: 2 AN: 974862 Hom.: 0 AF XY: 0.00000209 AC XY: 1 AN XY: 479124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000262

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000210 AC: 2 AN: 95022 Hom.: 0 Cov.: 26 AF XY: 0.0000223 AC XY: 1 AN XY: 44796

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000473

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;