1-22644042-TC-AA

Position:

• chr1-22644042-TC-AA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_172369.5(C1QC):​c.19_20delTCinsAA​(p.Ser7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QC NM_172369.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.159

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 1-22644042-TC-AA is Benign according to our data. Variant chr1-22644042-TC-AA is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 625896.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QC	NM_172369.5	c.19_20delTCinsAA	p.Ser7Asn	missense_variant		ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.19_20delTCinsAA	p.Ser7Asn	missense_variant			NP_001107573.1
C1QC	NM_001347619.2	c.19_20delTCinsAA	p.Ser7Asn	missense_variant			NP_001334548.1
C1QC	NM_001347620.2	c.-87+328_-87+329delTCinsAA		intron_variant			NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.19_20delTCinsAA	p.Ser7Asn	missense_variant		1	NM_172369.5	ENSP00000363771.4
ENSG00000289692	ENST00000695747.1	c.604_605delTCinsAA	p.Ser202Asn	missense_variant				ENSP00000512140.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

C1Q deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago

Jul 11, 2018

C1QC NM_001114101.2 exon 2 p.Ser7Asn (c.19_20delinsAA): This variant has not been reported in the literature and is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. This variant represents an in-frame deletion and insertion of 2 nucleotides, resulting in a single amino acid substitution at position 7 and is not predicted to alter the reading frame. However, the effect of this variant on the protein is unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1557603993; hg19: chr1-22970535;