Genetic Variant NM_172369.5:c.30C>A (chr1-22644053-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172369.5(C1QC):c.30C>A(p.His10Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,434,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H10H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

C1QC
NM_172369.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

0 publications found

Variant links:

Genes affected

C1QC (HGNC:1245): (complement C1q C chain) This gene encodes the C-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

C1QC Gene-Disease associations (from GenCC):

C1Q deficiency
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

C1QC links:

ENSG00000289692 (HGNC:):

ENSG00000289692 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09653443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172369.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QC	NM_172369.5	MANE Select	c.30C>A	p.His10Gln	missense	Exon 2 of 3	NP_758957.2	P02747
C1QC	NM_001114101.3		c.30C>A	p.His10Gln	missense	Exon 2 of 3	NP_001107573.1	P02747
C1QC	NM_001347619.2		c.30C>A	p.His10Gln	missense	Exon 2 of 3	NP_001334548.1	P02747

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C1QC	ENST00000374640.9	TSL:1 MANE Select	c.30C>A	p.His10Gln	missense	Exon 2 of 3	ENSP00000363771.4	P02747
ENSG00000289692	ENST00000695747.1		c.615C>A	p.His205Gln	missense	Exon 5 of 5	ENSP00000512140.1	A0A8Q3SI62
C1QC	ENST00000374637.1	TSL:3	c.30C>A	p.His10Gln	missense	Exon 2 of 3	ENSP00000363768.1	P02747

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000494

AC:

AN:

202442

AF XY:

0.00000921

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1434852

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33274

American (AMR)

AF:

0.00

AC:

AN:

39710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

38844

South Asian (SAS)

AF:

0.00

AC:

AN:

81610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51156

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

1100006

Other (OTH)

AF:

0.00

AC:

AN:

59462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

Cov.:

Alfa

AF:

0.0000312

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.5

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.076

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.26

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.097

MetaSVM

Benign

-0.69

MutationAssessor

Benign

0.20

PhyloP100

-1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.010

REVEL

Benign

0.11

Sift

Benign

0.48

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.061

MutPred

0.58

Gain of disorder (P = 0.0756)

MVP

0.80

MPC

0.32

ClinPred

0.030

GERP RS

0.53

PromoterAI

0.036

Neutral

(source)

Varity_R

0.040

gMVP

0.32

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over