Genetic Variant TEN1:c.92+8C>T (chr17-75986292-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001113324.3(TEN1):c.92+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00375 in 1,542,108 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts 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 Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0034 ( 19 hom. )

Consequence

TEN1
NM_001113324.3 splice_region, intron

Scores

Splicing: ADA: 0.0003173

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.663

Variant links:

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 links:

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]

TEN1-CDK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-75986292-C-T is Benign according to our data. Variant chr17-75986292-C-T is described in ClinVar as [Benign]. Clinvar id is 719572.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00662 (1006/152008) while in subpopulation AFR AF= 0.0167 (693/41456). AF 95% confidence interval is 0.0157. There are 5 homozygotes in gnomad4. There are 466 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEN1	NM_001113324.3 link	c.92+8C>T		splice_region_variant, intron_variant	Intron 2 of 3	ENST00000397640.6	NP_001106795.2	Q86WV5
TEN1-CDK3	NR_037709.1 link	n.393+8C>T		splice_region_variant, intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEN1	ENST00000397640.6 link	c.92+8C>T		splice_region_variant, intron_variant	Intron 2 of 3	1	NM_001113324.3	ENSP00000380762.1		Q86WV5
TEN1-CDK3	ENST00000649294.1 link	n.92+8C>T		splice_region_variant, intron_variant	Intron 2 of 10			ENSP00000497034.1

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1006

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0168

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00461

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000758

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00232

AC:

348

AN:

149802

Hom.:

AF XY:

0.00219

AC XY:

174

AN XY:

79460

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000141

Gnomad FIN exome

AF:

0.000119

Gnomad NFE exome

AF:

0.00270

Gnomad OTH exome

AF:

0.00121

GnomAD4 exome

AF:

0.00344

AC:

4776

AN:

1390100

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2212

AN XY:

685510

show subpopulations

Gnomad4 AFR exome

AF:

0.0158

Gnomad4 AMR exome

AF:

0.00234

Gnomad4 ASJ exome

AF:

0.0000799

Gnomad4 EAS exome

AF:

0.0000285

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.000204

Gnomad4 NFE exome

AF:

0.00367

Gnomad4 OTH exome

AF:

0.00396

GnomAD4 genome

AF:

0.00662

AC:

1006

AN:

152008

Hom.:

Cov.:

AF XY:

0.00627

AC XY:

466

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0167

Gnomad4 AMR

AF:

0.00460

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000758

Gnomad4 NFE

AF:

0.00337

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00479

Hom.:

Bravo

AF:

0.00689

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.35

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00032

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over