Genetic Variant ENST00000409178.5:n.2297T>G (chr10-73910185-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000409178.5(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
ENST00000409178.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.18

Publications

5 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=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
C10orf55	NR_160937.1 link	n.2426T>G	non_coding_transcript_exon_variant	Exon 6 of 6
C10orf55	NR_160938.1 link	n.2297T>G	non_coding_transcript_exon_variant	Exon 5 of 5
PLAU	NM_001441154.1 link	c.-32+891A>C	intron_variant	Intron 2 of 11	NP_001428083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
C10orf55	ENST00000409178.5 link	n.2297T>G	non_coding_transcript_exon_variant	Exon 5 of 5	1
PLAU	ENST00000481390.5 link	c.-32+891A>C	intron_variant	Intron 1 of 4	2	ENSP00000474318.1
C10orf55	ENST00000721915.1 link	n.269-1732T>G	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.0653

AC:

9939

AN:

152146

Hom.:

808

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.0654

AC:

9960

AN:

152264

Hom.:

814

Cov.:

AF XY:

0.0634

AC XY:

4720

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.194

AC:

8067

AN:

41516

American (AMR)

AF:

0.0312

AC:

477

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0265

AC:

AN:

3472

East Asian (EAS)

AF:

0.0557

AC:

289

AN:

5184

South Asian (SAS)

AF:

0.0427

AC:

206

AN:

4828

European-Finnish (FIN)

AF:

0.00480

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00994

AC:

676

AN:

68020

Other (OTH)

AF:

0.0445

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

405

811

1216

1622

2027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0432

Hom.:

683

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

(source)

DANN

Benign

0.81

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over