Genetic Variant C10orf55:n.215C>A (chr10-73909432-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.840

Publications

40 publications found

Variant links:

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]

C10orf55 links:

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)

PLAU links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAU	NM_001441154.1 link	c.-32+138G>T		intron_variant	Intron 2 of 11		NP_001428083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
C10orf55	ENST00000721923.1 link	n.215C>A	non_coding_transcript_exon_variant	Exon 1 of 2
PLAU	ENST00000481390.5 link	c.-32+138G>T	intron_variant	Intron 1 of 4	2	ENSP00000474318.1
C10orf55	ENST00000721915.1 link	n.269-979C>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99316

AN:

151922

Hom.:

33096

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.682

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.654

AC:

99368

AN:

152040

Hom.:

33111

Cov.:

AF XY:

0.646

AC XY:

48002

AN XY:

74308

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1713

3427

5140

6854

8567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.84

PromoterAI

-0.13

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over