chr6-43524804-T-TCCTTCCCCCATG

Position:

• chr6-43524804-T-TCCTTCCCCCATG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020750.3(XPO5):​c.3312+26_3312+27insCATGGGGGAAGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,611,432 control chromosomes in the GnomAD database, including 362 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (113 hom., cov: 32)
  • Exomes 𝑓: 0.015 (249 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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 -10 ACMG points.

• BP6: Variant 6-43524804-T-TCCTTCCCCCATG is Benign according to our data. Variant chr6-43524804-T-TCCTTCCCCCATG is described in ClinVar as [Benign]. Clinvar id is 1239542.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPO5	NM_020750.3	c.3312+26_3312+27insCATGGGGGAAGG		intron_variant		ENST00000265351.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPO5	ENST00000265351.12	c.3312+26_3312+27insCATGGGGGAAGG		intron_variant		1	NM_020750.3	P1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4052 AN: 152064 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0144

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0111 AC: 2757 AN: 248072 Hom.: 42 AF XY: 0.0103 AC XY: 1382 AN XY: 134554

Gnomad AFR exome AF: 0.0631

Gnomad AMR exome AF: 0.00421

Gnomad ASJ exome AF: 0.00561

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.00382

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0149 AC: 21807 AN: 1459252 Hom.: 249 Cov.: 33 AF XY: 0.0143 AC XY: 10376 AN XY: 725868

Gnomad4 AFR exome AF: 0.0678

Gnomad4 AMR exome AF: 0.00548

Gnomad4 ASJ exome AF: 0.00667

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00104

Gnomad4 FIN exome AF: 0.00411

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0268 AC: 4076 AN: 152180 Hom.: 113 Cov.: 32 AF XY: 0.0248 AC XY: 1842 AN XY: 74414

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00165

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0199

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

Jul 10, 2018

- -

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: rs369159546; hg19: chr6-43492542;