ENST00000721923.1:n.215C>A

Variant names:

• chr10-73909432-G-T
• rs2227551
• ENST00000721923.1:n.215C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000721923.1(C10orf55):​n.215C>A 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 0.654 in 152,070 control chromosomes in the GnomAD database, including 33,119 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 0.65 (33111 hom., cov: 32)
  • Exomes 𝑓: 0.67 (8 hom.)
• Consequence: C10orf55 ENST00000721923.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.840
• Publications: 40 publications found

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]

PLAU Gene-Disease associations (from GenCC):

• Quebec platelet disorder

  Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000721923.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAU	NM_001441154.1		c.-32+138G>T		intron	N/A	NP_001428083.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C10orf55	ENST00000721923.1		n.215C>A		non_coding_transcript_exon	Exon 1 of 2
	PLAU	ENST00000481390.5	TSL:2	c.-32+138G>T		intron	N/A	ENSP00000474318.1
	C10orf55	ENST00000721915.1		n.269-979C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99316 AN: 151922 Hom.: 33096 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.717

GnomAD4 exome AF: 0.667 AC: 20 AN: 30 Hom.: 8 AF XY: 0.667 AC XY: 16 AN XY: 24

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.682 AC: 15 AN: 22

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.654 AC: 99368 AN: 152040 Hom.: 33111 Cov.: 32 AF XY: 0.646 AC XY: 48002 AN XY: 74308

African (AFR) AF: 0.589 AC: 24407 AN: 41460

American (AMR) AF: 0.567 AC: 8654 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.871 AC: 3020 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2191 AN: 5148

South Asian (SAS) AF: 0.550 AC: 2653 AN: 4824

European-Finnish (FIN) AF: 0.622 AC: 6578 AN: 10574

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49502 AN: 67978

Other (OTH) AF: 0.709 AC: 1495 AN: 2108

Alfa AF: 0.702 Hom.: 79066

Bravo AF: 0.648

Asia WGS AF: 0.472 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.68
PhyloP100		0.84
PromoterAI		-0.13	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2227551; hg19: chr10-75669190;