rs3760132

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-75979390-C-A
• chr17-75979390-C-G
• chr17-75979390-C-T

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.-128C>A 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 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TEN1 NM_001113324.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: 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 (BayesDel_noAF=-0.69).

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>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001106795.2	Q86WV5
	TEN1	NM_001113324.3	MANE Select	c.-128C>A		5_prime_UTR	Exon 1 of 4	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.174C>A		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>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000380762.1	Q86WV5
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.-128C>A		5_prime_UTR	Exon 1 of 4	ENSP00000380762.1	Q86WV5
	TEN1-CDK3	ENST00000649294.1		n.-128C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000497034.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 351116 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 186012

African (AFR) AF: 0.00 AC: 0 AN: 9682

American (AMR) AF: 0.00 AC: 0 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10370

East Asian (EAS) AF: 0.00 AC: 0 AN: 21750

South Asian (SAS) AF: 0.00 AC: 0 AN: 43592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20730

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1488

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 208392

Other (OTH) AF: 0.00 AC: 0 AN: 19978

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152184 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74346

African (AFR) AF: 0.00 AC: 0 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.24
DANN	Benign	0.69
PhyloP100		-1.2
PromoterAI		0.0048	Neutral

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;