17-75991577-G-A

Variant names:

• chr17-75991577-G-A
• rs200875806
• NM_001113324.3:c.204G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001113324.3(TEN1):​c.204G>A​(p.Gln68Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,552,154 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (11 hom.)
• Consequence: TEN1 NM_001113324.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.279
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 17-75991577-G-A is Benign according to our data. Variant chr17-75991577-G-A is described in ClinVar as Benign. ClinVar VariationId is 734747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.279 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00109 (1520/1399834) while in subpopulation MID AF = 0.0268 (153/5702). AF 95% confidence interval is 0.0234. There are 11 homozygotes in GnomAdExome4. There are 814 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 11 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.204G>A	p.Gln68Gln	synonymous	Exon 3 of 4	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.505G>A		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.204G>A	p.Gln68Gln	synonymous	Exon 3 of 4	ENSP00000380762.1	Q86WV5
	TEN1-CDK3	ENST00000649294.1		n.204G>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000497034.1
	TEN1	ENST00000911175.1		c.204G>A	p.Gln68Gln	synonymous	Exon 4 of 5	ENSP00000581234.1

Frequencies

GnomAD3 genomes AF: 0.00104 AC: 158 AN: 152202 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00221 AC: 350 AN: 158064 AF XY: 0.00235

Gnomad AFR exome AF: 0.000609

Gnomad AMR exome AF: 0.00303

Gnomad ASJ exome AF: 0.0129

Gnomad EAS exome AF: 0.0000917

Gnomad FIN exome AF: 0.0000589

Gnomad NFE exome AF: 0.00132

Gnomad OTH exome AF: 0.00937

GnomAD4 exome AF: 0.00109 AC: 1520 AN: 1399834 Hom.: 11 Cov.: 31 AF XY: 0.00118 AC XY: 814 AN XY: 690398

African (AFR) AF: 0.00136 AC: 43 AN: 31598

American (AMR) AF: 0.00286 AC: 102 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 285 AN: 25180

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35738

South Asian (SAS) AF: 0.00164 AC: 130 AN: 79234

European-Finnish (FIN) AF: 0.0000404 AC: 2 AN: 49478

Middle Eastern (MID) AF: 0.0268 AC: 153 AN: 5702

European-Non Finnish (NFE) AF: 0.000598 AC: 645 AN: 1079058

Other (OTH) AF: 0.00273 AC: 159 AN: 58136

GnomAD4 genome AF: 0.00104 AC: 158 AN: 152320 Hom.: 0 Cov.: 31 AF XY: 0.000940 AC XY: 70 AN XY: 74474

African (AFR) AF: 0.000529 AC: 22 AN: 41574

American (AMR) AF: 0.00222 AC: 34 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10628

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68034

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00199 Hom.: 0

Bravo AF: 0.00134

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.28
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs200875806; hg19: chr17-73987658;