17-75979390-C-T

Position:

• chr17-75979390-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001113324.3(TEN1):​c.-128C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 503,226 control chromosomes in the GnomAD database, including 985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (267 hom., cov: 32)
  • Exomes 𝑓: 0.056 (718 hom.)
• Consequence: TEN1 NM_001113324.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.20

Genes affected

TEN1 (HGNC:37242): (TEN1 subunit of CST complex) C17ORF106, or TEN1, appears to function in a telomere-associated complex with STN1 (OBFC1; MIM 613128) and CTC1 (C17ORF68; MIM 613129) (Miyake et al., 2009 [PubMed 19854130]).[supplied by OMIM, Nov 2009]

TEN1-CDK3 (HGNC:44420): (TEN1-CDK3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TEN1 telomerase capping complex subunit homolog (S. cerevisiae) and cyclin-dependent kinase 3 (CDK3) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-75979390-C-T is Benign according to our data. Variant chr17-75979390-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 325396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEN1	NM_001113324.3	c.-128C>T		5_prime_UTR_premature_start_codon_gain_variant	1/4	ENST00000397640.6	NP_001106795.2
TEN1	NM_001113324.3	c.-128C>T		5_prime_UTR_variant	1/4	ENST00000397640.6	NP_001106795.2
TEN1-CDK3	NR_037709.1	n.174C>T		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEN1	ENST00000397640	c.-128C>T		5_prime_UTR_premature_start_codon_gain_variant	1/4	1	NM_001113324.3	ENSP00000380762.1
TEN1	ENST00000397640	c.-128C>T		5_prime_UTR_variant	1/4	1	NM_001113324.3	ENSP00000380762.1
TEN1-CDK3	ENST00000649294	n.-128C>T		5_prime_UTR_premature_start_codon_gain_variant	1/11			ENSP00000497034.1
TEN1-CDK3	ENST00000649294.1	n.-128C>T		non_coding_transcript_exon_variant	1/11			ENSP00000497034.1
TEN1-CDK3	ENST00000649294	n.-128C>T		5_prime_UTR_variant	1/11			ENSP00000497034.1

Frequencies

GnomAD3 genomes AF: 0.0562 AC: 8546 AN: 152172 Hom.: 266 Cov.: 32

Gnomad AFR AF: 0.0560

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0688

GnomAD4 exome AF: 0.0564 AC: 19783 AN: 350936 Hom.: 718 Cov.: 0 AF XY: 0.0546 AC XY: 10160 AN XY: 185934

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.0594

Gnomad4 ASJ exome AF: 0.0757

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0519

Gnomad4 NFE exome AF: 0.0517

Gnomad4 OTH exome AF: 0.0599

GnomAD4 genome AF: 0.0563 AC: 8571 AN: 152290 Hom.: 267 Cov.: 32 AF XY: 0.0542 AC XY: 4037 AN XY: 74468

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.0628

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0346

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0350 Hom.: 37

Bravo AF: 0.0604

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -

Acyl-CoA oxidase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.36
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs3760132; hg19: chr17-73975471;