rs2227553

Positions:

• chr10-73910185-A-C
• chr10-73910185-A-T

Variant summary

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

The NR_160938.1(C10orf55):​n.2297T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0654 in 152,264 control chromosomes in the GnomAD database, including 814 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 0.065 (814 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C10orf55 NR_160938.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

Genes affected

C10orf55 (HGNC:31008): (chromosome 10 putative open reading frame 55) Enables identical protein binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PLAU (HGNC:9052): (plasminogen activator, urokinase) This gene encodes a secreted serine protease that converts plasminogen to plasmin. The encoded preproprotein is proteolytically processed to generate A and B polypeptide chains. These chains associate via a single disulfide bond to form the catalytically inactive high molecular weight urokinase-type plasminogen activator (HMW-uPA). HMW-uPA can be further processed into the catalytically active low molecular weight urokinase-type plasminogen activator (LMW-uPA). This low molecular weight form does not bind to the urokinase-type plasminogen activator receptor. Mutations in this gene may be associated with Quebec platelet disorder and late-onset Alzheimer's disease. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C10orf55	NR_160938.1	n.2297T>G		non_coding_transcript_exon_variant	5/5
PLAU	XM_011539866.3	c.-32+891A>C		intron_variant
C10orf55	NR_160937.1	n.2426T>G		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C10orf55	ENST00000409178.5	n.2297T>G		non_coding_transcript_exon_variant	5/5	1
PLAU	ENST00000481390.5	c.-32+891A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9939 AN: 152146 Hom.: 808 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0313

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.0562

Gnomad SAS AF: 0.0426

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00994

Gnomad OTH AF: 0.0455

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 18 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0654 AC: 9960 AN: 152264 Hom.: 814 Cov.: 33 AF XY: 0.0634 AC XY: 4720 AN XY: 74452

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0312

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.0557

Gnomad4 SAS AF: 0.0427

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.00994

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0214 Hom.: 148

Bravo AF: 0.0735

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.81

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: rs2227553; hg19: chr10-75669943;