Genetic Variant NM_025099.6:c.13C>A (chr17-8248024-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_025099.6(CTC1):c.13C>A(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R5R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CTC1
NM_025099.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Publications

3 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 -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-1.73 with no splicing effect.

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
CTC1	NM_025099.6	MANE Select	c.13C>A	p.Arg5Arg	synonymous	Exon 1 of 23	NP_079375.3
CTC1	NM_001411067.1		c.13C>A	p.Arg5Arg	synonymous	Exon 1 of 21	NP_001397996.1
CTC1	NR_046431.2		n.33C>A		non_coding_transcript_exon	Exon 1 of 22

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CTC1	ENST00000651323.1	MANE Select	c.13C>A	p.Arg5Arg	synonymous	Exon 1 of 23	ENSP00000498499.1
CTC1	ENST00000581729.2	TSL:3	c.13C>A	p.Arg5Arg	synonymous	Exon 1 of 21	ENSP00000462720.2
CTC1	ENST00000580299.2	TSL:5	c.13C>A	p.Arg5Arg	synonymous	Exon 1 of 21	ENSP00000462607.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000425

AC:

AN:

235396

AF XY:

0.00000775

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000950

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1446264

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719174

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32808

American (AMR)

AF:

0.00

AC:

AN:

44094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25832

East Asian (EAS)

AF:

0.00

AC:

AN:

38984

South Asian (SAS)

AF:

0.00

AC:

AN:

85674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1104242

Other (OTH)

AF:

0.00

AC:

AN:

59274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.94

(source)

DANN

Benign

0.58

PhyloP100

-1.7

PromoterAI

-0.079

Neutral

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over