rs979798808

Variant names:

• chr17-8248006-A-G
• rs979798808
• NM_025099.6:c.31T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025099.6(CTC1):​c.31T>C​(p.Ser11Pro) variant causes a missense, splice region 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. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. S11C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CTC1 NM_025099.6 missense, splice_region
• Scores: Splicing: ADA: 0.0001180
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.201
• Publications: 1 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]

PFAS (HGNC:8863): (phosphoribosylformylglycinamidine synthase) Purines are necessary for many cellular processes, including DNA replication, transcription, and energy metabolism. Ten enzymatic steps are required to synthesize inosine monophosphate (IMP) in the de novo pathway of purine biosynthesis. The enzyme encoded by this gene catalyzes the fourth step of IMP biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20900765).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6	c.31T>C	p.Ser11Pro	missense_variant, splice_region_variant	Exon 1 of 23	ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1	c.31T>C	p.Ser11Pro	missense_variant, splice_region_variant	Exon 1 of 23		NM_025099.6	ENSP00000498499.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31T>C (p.S11P) alteration is located in exon 1 (coding exon 1) of the CTC1 gene. This alteration results from a T to C substitution at nucleotide position 31, causing the serine (S) at amino acid position 11 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Benign	0.81
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.20
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.87	N
REVEL	Uncertain	0.41
Sift	Benign	0.055	T
Sift4G	Benign	0.074	T
Polyphen		0.91	P
Vest4		0.35
MutPred		0.20		Gain of glycosylation at S10 (P = 0.0647);
MVP		0.42
MPC		0.17
ClinPred		0.41	T
GERP RS		1.7
PromoterAI		-0.15	Neutral
Varity_R		0.21
gMVP		0.46
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.054
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs979798808; hg19: chr17-8151324;