6-24667095-C-A

Variant names:

• chr6-24667095-C-A
• rs17243157
• NM_018473.4:c.-169C>A

Variant summary

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

The NM_018473.4(ACOT13):​c.-169C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOT13 NM_018473.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 0 publications found

Genes affected

ACOT13 (HGNC:20999): (acyl-CoA thioesterase 13) This gene encodes a member of the thioesterase superfamily. In humans, the protein co-localizes with microtubules and is essential for sustained cell proliferation. The orthologous mouse protein forms a homotetramer and is associated with mitochondria. The mouse protein functions as a medium- and long-chain acyl-CoA thioesterase. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2009]

TDP2 (HGNC:17768): (tyrosyl-DNA phosphodiesterase 2) This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors. [provided by RefSeq, Jul 2008]

TDP2 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 23

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

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=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT13	NM_018473.4	MANE Select	c.-169C>A		5_prime_UTR	Exon 1 of 3	NP_060943.1
	ACOT13	NM_001160094.2		c.-527C>A		5_prime_UTR	Exon 1 of 4	NP_001153566.1
	TDP2	NM_016614.3	MANE Select	c.-233G>T		upstream_gene	N/A	NP_057698.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT13	ENST00000230048.5	TSL:1 MANE Select	c.-169C>A		5_prime_UTR	Exon 1 of 3	ENSP00000230048.3
	ACOT13	ENST00000537591.5	TSL:1	c.-527C>A		5_prime_UTR	Exon 1 of 4	ENSP00000445552.1
	TDP2	ENST00000378198.9	TSL:1 MANE Select	c.-233G>T		upstream_gene	N/A	ENSP00000367440.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 695338 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 356818

African (AFR) AF: 0.00 AC: 0 AN: 17166

American (AMR) AF: 0.00 AC: 0 AN: 19992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15574

East Asian (EAS) AF: 0.00 AC: 0 AN: 32376

South Asian (SAS) AF: 0.00 AC: 0 AN: 52440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32894

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2502

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 488268

Other (OTH) AF: 0.00 AC: 0 AN: 34126

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-1.6
PromoterAI		0.12	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: rs17243157; hg19: chr6-24667323;