6-43523703-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020750.3(XPO5):c.*165G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00868 in 1,058,394 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (339 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (212 hom.)
• Consequence: XPO5 NM_020750.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.294

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 6-43523703-C-T is Benign according to our data. Variant chr6-43523703-C-T is described in ClinVar as [Benign]. Clinvar id is 1178765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO5	NM_020750.3	c.*165G>A		3_prime_UTR_variant	32/32	ENST00000265351.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO5	ENST00000265351.12	c.*165G>A		3_prime_UTR_variant	32/32	1	NM_020750.3	P1

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5448 AN: 152162 Hom.: 338 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0283

GnomAD3 exomes AF: 0.00891 AC: 2197 AN: 246472 Hom.: 136 AF XY: 0.00680 AC XY: 913 AN XY: 134324

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.00646

Gnomad ASJ exome AF: 0.000902

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000324

Gnomad OTH exome AF: 0.00365

GnomAD4 exome AF: 0.00412 AC: 3731 AN: 906114 Hom.: 212 Cov.: 13 AF XY: 0.00348 AC XY: 1649 AN XY: 474430

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.00711

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000268

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000241

Gnomad4 OTH exome AF: 0.00831

GnomAD4 genome AF: 0.0359 AC: 5461 AN: 152280 Hom.: 339 Cov.: 32 AF XY: 0.0346 AC XY: 2581 AN XY: 74488

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000544

Gnomad4 OTH AF: 0.0280

Alfa AF: 0.00977 Hom.: 111

Bravo AF: 0.0404

Asia WGS AF: 0.00664 AC: 23 AN: 3478

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

Oct 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	8.2
Dann	Benign	0.86

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: rs7759854; hg19: chr6-43491441;