Genetic Variant CTC1:p.Ser10Ala (chr17-8248009-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025099.6(CTC1):c.28T>G(p.Ser10Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,411,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. S10F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

CTC1
NM_025099.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

0 publications found

Variant links:

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 links:

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]

PFAS links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043726623).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTC1	NM_025099.6	MANE Select	c.28T>G	p.Ser10Ala	missense	Exon 1 of 23	NP_079375.3
CTC1	NM_001411067.1		c.28T>G	p.Ser10Ala	missense	Exon 1 of 21	NP_001397996.1	J3KSZ1
CTC1	NR_046431.2		n.48T>G		non_coding_transcript_exon	Exon 1 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTC1	ENST00000651323.1	MANE Select	c.28T>G	p.Ser10Ala	missense	Exon 1 of 23	ENSP00000498499.1	Q2NKJ3-1
CTC1	ENST00000699849.1		c.-706T>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 20	ENSP00000514647.1	A0A8V8TQN9
CTC1	ENST00000932859.1		c.28T>G	p.Ser10Ala	missense	Exon 1 of 23	ENSP00000602918.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1411450

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

701354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31958

American (AMR)

AF:

0.00

AC:

AN:

42966

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24350

East Asian (EAS)

AF:

0.00

AC:

AN:

36284

South Asian (SAS)

AF:

0.00

AC:

AN:

85398

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5496

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078864

Other (OTH)

AF:

0.00

AC:

AN:

56980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.052

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.011

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.18

M_CAP

Benign

0.059

MetaRNN

Benign

0.044

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.69

PhyloP100

-1.5

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.23

REVEL

Benign

0.11

Sift

Benign

0.68

Sift4G

Benign

0.45

Polyphen

0.0020

Vest4

0.16

MutPred

0.17

Loss of loop (P = 0.0203)

MVP

0.29

MPC

0.097

ClinPred

0.051

GERP RS

-4.2

PromoterAI

-0.071

Neutral

(source)

Varity_R

0.029

gMVP

0.16

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over