chr17-8232385-C-A

Variant names:

• chr17-8232385-C-A
• NM_025099.6:c.2036G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025099.6(CTC1):​c.2036G>T​(p.Gly679Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CTC1 NM_025099.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23432565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6	c.2036G>T	p.Gly679Val	missense_variant	Exon 12 of 23	ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1	c.2036G>T	p.Gly679Val	missense_variant	Exon 12 of 23		NM_025099.6	ENSP00000498499.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.0052	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.29
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.012	D
Polyphen		0.81	P
Vest4		0.34
MutPred		0.21		Loss of disorder (P = 0.1001);
MVP		0.46
MPC		0.31
ClinPred		0.70	D
GERP RS		-0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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: chr17-8135703;