12-7070184-CGG-GGT

Variant names:

• chr12-7070184-CGG-GGT
• NM_001734.5:c.1600_1602delCGGinsGGT
• C1S p.Arg534Gly

Variant summary

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

The NM_001734.5(C1S):​c.1600_1602delCGGinsGGT​(p.Arg534Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R534Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1S NM_001734.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 0 publications found

Genes affected

C1S (HGNC:1247): (complement C1s) This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]

C1S Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, periodontal type 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• complement component C1s deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Ehlers-Danlos syndrome, periodontitis type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001734.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1S	NM_001734.5	MANE Select	c.1600_1602delCGGinsGGT	p.Arg534Gly	missense	N/A	NP_001725.1	P09871
	C1S	NM_201442.4		c.1600_1602delCGGinsGGT	p.Arg534Gly	missense	N/A	NP_958850.1	P09871
	C1S	NM_001346850.2		c.1099_1101delCGGinsGGT	p.Arg367Gly	missense	N/A	NP_001333779.1	F8WCZ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1S	ENST00000360817.10	TSL:1 MANE Select	c.1600_1602delCGGinsGGT	p.Arg534Gly	missense	N/A	ENSP00000354057.5	P09871
	C1S	ENST00000328916.7	TSL:1	c.1600_1602delCGGinsGGT	p.Arg534Gly	missense	N/A	ENSP00000328173.3	P09871
	C1S	ENST00000402681.7	TSL:1	c.1099_1101delCGGinsGGT	p.Arg367Gly	missense	N/A	ENSP00000384171.3	F8WCZ6

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-7177488;