1-22644042-T-AA

Position:

• chr1-22644042-T-AA

Variant summary

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

The NM_172369.5(C1QC):​c.19delTinsAA​(p.Ser7fs) variant causes a frameshift, 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1QC NM_172369.5 frameshift, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U: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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QC	NM_172369.5	c.19delTinsAA	p.Ser7fs	frameshift_variant, missense_variant	2/3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.19delTinsAA	p.Ser7fs	frameshift_variant, missense_variant	2/3		NP_001107573.1
C1QC	NM_001347619.2	c.19delTinsAA	p.Ser7fs	frameshift_variant, missense_variant	2/3		NP_001334548.1
C1QC	NM_001347620.2	c.-87+328delTinsAA		intron_variant			NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.19delTinsAA	p.Ser7fs	frameshift_variant, missense_variant	2/3	1	NM_172369.5	ENSP00000363771.4
ENSG00000289692	ENST00000695747.1	c.604delTinsAA	p.Ser202fs	frameshift_variant, missense_variant	5/5			ENSP00000512140.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

Mar 30, 2021

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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-22970535;