Variant 17-5433041-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5

The NM_001212.4(C1QBP):c.823C>T(p.Leu275Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

C1QBP
NM_001212.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 9.84

Variant links:

Genes affected

C1QBP (HGNC:1243): (complement C1q binding protein) The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein. [provided by RefSeq, Jul 2008]

C1QBP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

PP5

Variant 17-5433041-G-A is Pathogenic according to our data. Variant chr17-5433041-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 441245.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QBP	NM_001212.4 linkuse as main transcript	c.823C>T	p.Leu275Phe	missense_variant	6/6	ENST00000225698.8	NP_001203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C1QBP	ENST00000225698.8 linkuse as main transcript	c.823C>T	p.Leu275Phe	missense_variant	6/6	1	NM_001212.4	ENSP00000225698	P1
C1QBP	ENST00000574444.5 linkuse as main transcript	c.511C>T	p.Leu171Phe	missense_variant	6/6	3		ENSP00000460308
C1QBP	ENST00000570805.1 linkuse as main transcript	c.511C>T	p.Leu171Phe	missense_variant	6/6	3		ENSP00000460638
C1QBP	ENST00000573204.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Combined oxidative phosphorylation deficiency 33

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;.;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.072

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

0.018

MutationAssessor

Uncertain

2.7

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-3.5

D;.;.

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0040

D;.;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.98

D;.;.

Vest4

0.82

MutPred

0.75

Gain of methylation at K276 (P = 0.0562);.;.;

MVP

0.57

MPC

1.0

ClinPred

0.97

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.82

gMVP

0.87

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over