chr6-43524732-AT-A

Variant names:

• chr6-43524732-AT-A
• rs150762267
• NM_020750.3:c.3312+98delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_020750.3(XPO5):​c.3312+98delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00661 in 1,586,570 control chromosomes in the GnomAD database, including 620 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (342 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (278 hom.)
• Consequence: XPO5 NM_020750.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.14
• Publications: 1 publications found

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]

POLR1C Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 11

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Treacher Collins syndrome 3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Treacher-Collins syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-43524732-AT-A is Benign according to our data. Variant chr6-43524732-AT-A is described in ClinVar as Benign. ClinVar VariationId is 1251623.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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020750.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO5	NM_020750.3	MANE Select	c.3312+98delA		intron	N/A	NP_065801.1	Q9HAV4
	POLR1C	NM_001318876.2		c.922+3687delT		intron	N/A	NP_001305805.1	O15160-2
	POLR1C	NM_001363658.2		c.922+3687delT		intron	N/A	NP_001350587.1	A0A2R8YEZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPO5	ENST00000265351.12	TSL:1 MANE Select	c.3312+98delA		intron	N/A	ENSP00000265351.7	Q9HAV4
	POLR1C	ENST00000304004.7	TSL:1	c.922+3685delT		intron	N/A	ENSP00000307212.3	O15160-2
	XPO5	ENST00000943409.1		c.3309+98delA		intron	N/A	ENSP00000613468.1

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5455 AN: 152132 Hom.: 341 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: 0.0282

GnomAD4 exome AF: 0.00349 AC: 5012 AN: 1434320 Hom.: 278 Cov.: 33 AF XY: 0.00308 AC XY: 2191 AN XY: 710308

African (AFR) AF: 0.122 AC: 4005 AN: 32738

American (AMR) AF: 0.00693 AC: 294 AN: 42414

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 36 AN: 24184

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.000244 AC: 20 AN: 81990

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52366

Middle Eastern (MID) AF: 0.00295 AC: 14 AN: 4748

European-Non Finnish (NFE) AF: 0.000177 AC: 194 AN: 1097392

Other (OTH) AF: 0.00758 AC: 448 AN: 59070

GnomAD4 genome AF: 0.0359 AC: 5468 AN: 152250 Hom.: 342 Cov.: 32 AF XY: 0.0347 AC XY: 2580 AN XY: 74440

African (AFR) AF: 0.125 AC: 5179 AN: 41530

American (AMR) AF: 0.0122 AC: 187 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68014

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0321 Hom.: 19

Bravo AF: 0.0404

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs150762267; hg19: chr6-43492470;