chr17-75979246-G-A

Variant names:

• chr17-75979246-G-A
• rs575138461
• NM_001113324.3:c.-272G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001113324.3(TEN1):​c.-272G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000702 in 868,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: TEN1 NM_001113324.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.328
• Publications: 0 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]

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]

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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

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.-272G>A		5_prime_UTR	Exon 1 of 4	NP_001106795.2	Q86WV5
	TEN1-CDK3	NR_037709.1		n.30G>A		non_coding_transcript_exon	Exon 1 of 10
	ACOX1	NM_004035.7	MANE Select	c.-173C>T		upstream_gene	N/A	NP_004026.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEN1	ENST00000397640.6	TSL:1 MANE Select	c.-272G>A		5_prime_UTR	Exon 1 of 4	ENSP00000380762.1	Q86WV5
	ACOX1	ENST00000949477.1		c.-173C>T		5_prime_UTR	Exon 1 of 16	ENSP00000619536.1
	ACOX1	ENST00000911075.1		c.-173C>T		5_prime_UTR	Exon 1 of 13	ENSP00000581134.1

Frequencies

GnomAD3 genomes AF: 0.0000788 AC: 12 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000684 AC: 49 AN: 716420 Hom.: 0 Cov.: 9 AF XY: 0.0000697 AC XY: 26 AN XY: 372950

African (AFR) AF: 0.00 AC: 0 AN: 18606

American (AMR) AF: 0.000126 AC: 4 AN: 31736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18794

East Asian (EAS) AF: 0.000400 AC: 13 AN: 32514

South Asian (SAS) AF: 0.000147 AC: 9 AN: 61194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31916

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2870

European-Non Finnish (NFE) AF: 0.0000434 AC: 21 AN: 483362

Other (OTH) AF: 0.0000565 AC: 2 AN: 35428

GnomAD4 genome AF: 0.0000788 AC: 12 AN: 152324 Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74488

African (AFR) AF: 0.00 AC: 0 AN: 41580

American (AMR) AF: 0.000131 AC: 2 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000604

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Acyl-CoA oxidase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		0.33
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs575138461; hg19: chr17-73975327;