17-75979390-C-T

Variant names:

• chr17-75979390-C-T
• rs3760132
• NM_001113324.3:c.-128C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACOX1 Gene-Disease associations (from GenCC):

• peroxisomal acyl-CoA oxidase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen, Ambry Genetics
• Mitchell syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

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.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001106795.2	Q86WV5
	TEN1	NM_001113324.3	MANE Select	c.-128C>T		5_prime_UTR	Exon 1 of 4	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.174C>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000380762.1	Q86WV5
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.-128C>T		5_prime_UTR	Exon 1 of 4	ENSP00000380762.1	Q86WV5
	TEN1-CDK3	ENST00000649294.1		n.-128C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 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

African (AFR) AF: 0.0545 AC: 528 AN: 9680

American (AMR) AF: 0.0594 AC: 899 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.0757 AC: 785 AN: 10364

East Asian (EAS) AF: 0.132 AC: 2873 AN: 21724

South Asian (SAS) AF: 0.0348 AC: 1518 AN: 43578

European-Finnish (FIN) AF: 0.0519 AC: 1076 AN: 20718

Middle Eastern (MID) AF: 0.0907 AC: 135 AN: 1488

European-Non Finnish (NFE) AF: 0.0517 AC: 10773 AN: 208284

Other (OTH) AF: 0.0599 AC: 1196 AN: 19970

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

African (AFR) AF: 0.0562 AC: 2337 AN: 41560

American (AMR) AF: 0.0628 AC: 960 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3470

East Asian (EAS) AF: 0.134 AC: 692 AN: 5162

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4830

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10624

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0511 AC: 3478 AN: 68026

Other (OTH) AF: 0.0733 AC: 155 AN: 2116

Alfa AF: 0.0350 Hom.: 37

Bravo AF: 0.0604

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Acyl-CoA oxidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.36
DANN	Benign	0.78
PhyloP100		-1.2
PromoterAI		-0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs3760132; hg19: chr17-73975471;