1-22644041-C-A

Variant names:

• chr1-22644041-C-A
• rs767376934
• NM_172369.5:c.18C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172369.5(C1QC):​c.18C>A​(p.Ser6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. S6S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: C1QC NM_172369.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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]

ENSG00000289692 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13330191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.18C>A	p.Ser6Arg	missense_variant	Exon 2 of 3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.18C>A	p.Ser6Arg	missense_variant	Exon 2 of 3		NP_001107573.1
C1QC	NM_001347619.2	c.18C>A	p.Ser6Arg	missense_variant	Exon 2 of 3		NP_001334548.1
C1QC	NM_001347620.2	c.-87+327C>A		intron_variant	Intron 1 of 1		NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.18C>A	p.Ser6Arg	missense_variant	Exon 2 of 3	1	NM_172369.5	ENSP00000363771.4
ENSG00000289692	ENST00000695747.1	c.603C>A	p.Ser201Arg	missense_variant	Exon 5 of 5			ENSP00000512140.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000489 AC: 1 AN: 204572 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 109768

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000346

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436240 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 711576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000249

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.46	.;.;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.41	N;N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0070	D;D;D
Sift4G	Benign	0.061	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.14
MutPred		0.20		Loss of phosphorylation at S6 (P = 0.0436);Loss of phosphorylation at S6 (P = 0.0436);Loss of phosphorylation at S6 (P = 0.0436);
MVP		0.83
MPC		0.55
ClinPred		0.088	T
GERP RS		1.3
Varity_R		0.044
gMVP		0.45

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

Other links and lift over

dbSNP: rs767376934; hg19: chr1-22970534;