17-75991577-G-C

Variant names:

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

Variant summary

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

The NM_001113324.3(TEN1):​c.204G>C​(p.Gln68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,399,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q68Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: TEN1 NM_001113324.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.026440889).

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>C	p.Gln68His	missense	Exon 3 of 4	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.505G>C		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>C	p.Gln68His	missense	Exon 3 of 4	ENSP00000380762.1	Q86WV5
	TEN1-CDK3	ENST00000649294.1		n.204G>C		non_coding_transcript_exon	Exon 3 of 11	ENSP00000497034.1
	TEN1	ENST00000911175.1		c.204G>C	p.Gln68His	missense	Exon 4 of 5	ENSP00000581234.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000127 AC: 2 AN: 158064 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000404

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000929 AC: 13 AN: 1399836 Hom.: 0 Cov.: 31 AF XY: 0.00000579 AC XY: 4 AN XY: 690398

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.0000280 AC: 1 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.000357 AC: 9 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079058

Other (OTH) AF: 0.0000172 AC: 1 AN: 58136

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.70
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.28
PROVEAN	Benign	0.0	N
REVEL	Benign	0.016
Sift	Benign	0.78	T
Sift4G	Benign	0.78	T
Vest4		0.13
MVP		0.014
ClinPred		0.036	T
GERP RS		-1.4
Varity_R		0.14
gMVP		0.45
Mutation Taster		=74/26	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;