NM_001113324.3:c.92+8C>T

Variant names:

• chr17-75986292-C-T
• rs74844461
• NM_001113324.3:c.92+8C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113324.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEN1	NM_001113324.3	MANE Select	c.92+8C>T		splice_region intron	N/A	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.393+8C>T		splice_region intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.92+8C>T		splice_region intron	N/A	ENSP00000380762.1	Q86WV5
	TEN1-CDK3	ENST00000649294.1		n.92+8C>T		splice_region intron	N/A	ENSP00000497034.1
	TEN1	ENST00000911175.1		c.92+8C>T		splice_region intron	N/A	ENSP00000581234.1

Frequencies

GnomAD3 genomes AF: 0.00662 AC: 1006 AN: 151890 Hom.: 5 Cov.: 31

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

GnomAD2 exomes AF: 0.00232 AC: 348 AN: 149802 AF XY: 0.00219

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 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.: 19 Cov.: 30 AF XY: 0.00323 AC XY: 2212 AN XY: 685510

African (AFR) AF: 0.0158 AC: 492 AN: 31184

American (AMR) AF: 0.00234 AC: 81 AN: 34542

Ashkenazi Jewish (ASJ) AF: 0.0000799 AC: 2 AN: 25026

East Asian (EAS) AF: 0.0000285 AC: 1 AN: 35122

South Asian (SAS) AF: 0.000129 AC: 10 AN: 77518

European-Finnish (FIN) AF: 0.000204 AC: 10 AN: 49082

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5670

European-Non Finnish (NFE) AF: 0.00367 AC: 3944 AN: 1074380

Other (OTH) AF: 0.00396 AC: 228 AN: 57576

GnomAD4 genome AF: 0.00662 AC: 1006 AN: 152008 Hom.: 5 Cov.: 31 AF XY: 0.00627 AC XY: 466 AN XY: 74308

African (AFR) AF: 0.0167 AC: 693 AN: 41456

American (AMR) AF: 0.00460 AC: 70 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000758 AC: 8 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00337 AC: 229 AN: 67996

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.00458 Hom.: 4

Bravo AF: 0.00689

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.35
DANN	Benign	0.50
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs74844461; hg19: chr17-73982373;