6-24667095-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018473.4(ACOT13):​c.-169C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 847,006 control chromosomes in the GnomAD database, including 6,313 homozygotes. 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 0.10 (884 hom., cov: 34)
  • Exomes 𝑓: 0.12 (5429 hom.)
• Consequence: ACOT13 NM_018473.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 23 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

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>T		5_prime_UTR	Exon 1 of 3	NP_060943.1
	ACOT13	NM_001160094.2		c.-527C>T		5_prime_UTR	Exon 1 of 4	NP_001153566.1
	TDP2	NM_016614.3	MANE Select	c.-233G>A		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>T		5_prime_UTR	Exon 1 of 3	ENSP00000230048.3
	ACOT13	ENST00000537591.5	TSL:1	c.-527C>T		5_prime_UTR	Exon 1 of 4	ENSP00000445552.1
	TDP2	ENST00000378198.9	TSL:1 MANE Select	c.-233G>A		upstream_gene	N/A	ENSP00000367440.4

Frequencies

GnomAD3 genomes AF: 0.100 AC: 15246 AN: 152066 Hom.: 885 Cov.: 34

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.117 AC: 81617 AN: 694820 Hom.: 5429 Cov.: 9 AF XY: 0.123 AC XY: 43820 AN XY: 356554

African (AFR) AF: 0.0596 AC: 1022 AN: 17156

American (AMR) AF: 0.0834 AC: 1667 AN: 19988

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 1997 AN: 15568

East Asian (EAS) AF: 0.102 AC: 3297 AN: 32370

South Asian (SAS) AF: 0.236 AC: 12366 AN: 52418

European-Finnish (FIN) AF: 0.0928 AC: 3051 AN: 32880

Middle Eastern (MID) AF: 0.175 AC: 438 AN: 2498

European-Non Finnish (NFE) AF: 0.110 AC: 53702 AN: 487842

Other (OTH) AF: 0.120 AC: 4077 AN: 34100

GnomAD4 genome AF: 0.100 AC: 15236 AN: 152186 Hom.: 884 Cov.: 34 AF XY: 0.100 AC XY: 7464 AN XY: 74412

African (AFR) AF: 0.0633 AC: 2624 AN: 41462

American (AMR) AF: 0.0909 AC: 1391 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3468

East Asian (EAS) AF: 0.0911 AC: 470 AN: 5160

South Asian (SAS) AF: 0.246 AC: 1189 AN: 4824

European-Finnish (FIN) AF: 0.0911 AC: 968 AN: 10624

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7611 AN: 68022

Other (OTH) AF: 0.105 AC: 221 AN: 2112

Alfa AF: 0.109 Hom.: 1454

Bravo AF: 0.0959

Asia WGS AF: 0.163 AC: 568 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.7
DANN	Benign	0.77
PhyloP100		-1.6
PromoterAI		0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs17243157; hg19: chr6-24667323; COSMIC: COSV57765608; COSMIC: COSV57765608;