NM_025099.6:c.33+9T>G

Variant names:

• chr17-8247995-A-C
• rs373483074
• NM_025099.6:c.33+9T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_025099.6(CTC1):​c.33+9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,412,918 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: CTC1 NM_025099.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.416
• 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]

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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-8247995-A-C is Benign according to our data. Variant chr17-8247995-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1123223.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTC1	NM_025099.6	c.33+9T>G		intron_variant	Intron 1 of 22	ENST00000651323.1	NP_079375.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTC1	ENST00000651323.1	c.33+9T>G		intron_variant	Intron 1 of 22		NM_025099.6	ENSP00000498499.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1412918 Hom.: 1 Cov.: 31 AF XY: 0.00000427 AC XY: 3 AN XY: 701988

African (AFR) AF: 0.00 AC: 0 AN: 32146

American (AMR) AF: 0.00 AC: 0 AN: 42996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24480

East Asian (EAS) AF: 0.0000570 AC: 2 AN: 35090

South Asian (SAS) AF: 0.00 AC: 0 AN: 85336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1080668

Other (OTH) AF: 0.00 AC: 0 AN: 57272

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dyskeratosis congenita Benign:1

Jul 08, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.3
DANN	Benign	0.79
PhyloP100		-0.42
PromoterAI		0.094	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs373483074; hg19: chr17-8151313;