chr17-8243157-A-C

Variant names:

• chr17-8243157-A-C
• rs201195157
• NM_025099.6:c.34-9T>G

Variant summary

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

The NM_025099.6(CTC1):​c.34-9T>G variant causes a intron change. The variant allele was found at a frequency of 0.000452 in 1,609,292 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: CTC1 NM_025099.6 intron
• Scores: Splicing: ADA: 0.9722
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4 B:1
• Conservation: PhyloP100: 4.32
• 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):

• cerebroretinal microangiopathy with calcifications and cysts 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
• dyskeratosis congenita

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• 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.34-9T>G		intron	N/A	NP_079375.3
	CTC1	NM_001411067.1		c.34-9T>G		intron	N/A	NP_001397996.1
	CTC1	NR_046431.2		n.54-9T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTC1	ENST00000651323.1	MANE Select	c.34-9T>G		intron	N/A	ENSP00000498499.1
	CTC1	ENST00000932859.1		c.34-9T>G		intron	N/A	ENSP00000602918.1
	CTC1	ENST00000968384.1		c.34-9T>G		intron	N/A	ENSP00000638443.1

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152218 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000289 AC: 70 AN: 242194 AF XY: 0.000380

Gnomad AFR exome AF: 0.000133

Gnomad AMR exome AF: 0.000122

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000471 AC: 686 AN: 1456956 Hom.: 1 Cov.: 30 AF XY: 0.000483 AC XY: 350 AN XY: 724906

African (AFR) AF: 0.0000603 AC: 2 AN: 33168

American (AMR) AF: 0.000184 AC: 8 AN: 43590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.000853 AC: 73 AN: 85554

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53340

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5730

European-Non Finnish (NFE) AF: 0.000504 AC: 559 AN: 1110046

Other (OTH) AF: 0.000548 AC: 33 AN: 60174

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152336 Hom.: 0 Cov.: 31 AF XY: 0.000255 AC XY: 19 AN XY: 74506

African (AFR) AF: 0.000144 AC: 6 AN: 41580

American (AMR) AF: 0.000262 AC: 4 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68036

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000272

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	2	-	Cerebroretinal microangiopathy with calcifications and cysts 1 (2)
-	1	1	Dyskeratosis congenita (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Benign	0.91
PhyloP100		4.3
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.97
dbscSNV1_RF	Benign	0.64
SpliceAI score (max)		0.26		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.26		Position offset: -9

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

Other links and lift over

dbSNP: rs201195157; hg19: chr17-8146475;