6-43523209-T-G

Position:

• chr6-43523209-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020750.3(XPO5):​c.*659A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 170,988 control chromosomes in the GnomAD database, including 19,258 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (17667 hom., cov: 32)
  • Exomes 𝑓: 0.38 (1591 hom.)
• Consequence: XPO5 NM_020750.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPO5	NM_020750.3	c.*659A>C		3_prime_UTR_variant	32/32	ENST00000265351.12	NP_065801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPO5	ENST00000265351.12	c.*659A>C		3_prime_UTR_variant	32/32	1	NM_020750.3	ENSP00000265351	P1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70693 AN: 151938 Hom.: 17637 Cov.: 32

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.383 AC: 7256 AN: 18932 Hom.: 1591 Cov.: 0 AF XY: 0.387 AC XY: 3850 AN XY: 9950

Gnomad4 AFR exome AF: 0.629

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.345

Gnomad4 EAS exome AF: 0.0627

Gnomad4 SAS exome AF: 0.410

Gnomad4 FIN exome AF: 0.414

Gnomad4 NFE exome AF: 0.411

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.466 AC: 70783 AN: 152056 Hom.: 17667 Cov.: 32 AF XY: 0.465 AC XY: 34516 AN XY: 74306

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.0654

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.429

Alfa AF: 0.429 Hom.: 13529

Bravo AF: 0.470

Asia WGS AF: 0.263 AC: 917 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.7
DANN	Benign	0.78

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: rs11077; hg19: chr6-43490947;