17-8232384-GC-AT

Variant names:

• chr17-8232384-GC-AT
• NM_025099.6:c.2036_2037delGCinsAT
• CTC1 p.Gly679Asp

Variant summary

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

The NM_025099.6(CTC1):​c.2036_2037delGCinsAT​(p.Gly679Asp) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G679A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTC1 NM_025099.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 0 publications found

Genes affected

CTC1 (HGNC:26169): (CST telomere replication complex component 1) This gene encodes a component of the CST complex. This complex plays an essential role in protecting telomeres from degradation. This protein also forms a heterodimer with the CST complex subunit STN1 to form the enzyme alpha accessory factor. This enzyme regulates DNA replication. Mutations in this gene are the cause of cerebroretinal microangiopathy with calcifications and cysts. Alternate splicing results in both coding and non-coding variants. [provided by RefSeq, Mar 2012]

CTC1 Gene-Disease associations (from GenCC):

• dyskeratosis congenita

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• cerebroretinal microangiopathy with calcifications and cysts 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Coats plus syndrome

  Inheritance: AR 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_025099.6. 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
	CTC1	NM_025099.6	MANE Select	c.2036_2037delGCinsAT	p.Gly679Asp	missense	N/A	NP_079375.3
	CTC1	NM_001411067.1		c.2036_2037delGCinsAT	p.Gly679Asp	missense	N/A	NP_001397996.1	J3KSZ1
	CTC1	NR_046431.2		n.1951_1952delGCinsAT		non_coding_transcript_exon	Exon 12 of 22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.2036_2037delGCinsAT	p.Gly679Asp	missense	N/A	ENSP00000498499.1	Q2NKJ3-1
	CTC1	ENST00000932859.1		c.2036_2037delGCinsAT	p.Gly679Asp	missense	N/A	ENSP00000602918.1
	CTC1	ENST00000968384.1		c.2036_2037delGCinsAT	p.Gly679Asp	missense	N/A	ENSP00000638443.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.68

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: chr17-8135702;