14-73537589-C-T

Variant names:

• chr14-73537589-C-T
• rs779044350
• NM_001037161.2:c.168C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001037161.2(ACOT1):​c.168C>T​(p.Thr56Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (69 hom., cov: 19)
  • Exomes 𝑓: 0.00048 (158 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACOT1 NM_001037161.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.185
• Publications: 0 publications found

Genes affected

ACOT1 (HGNC:33128): (acyl-CoA thioesterase 1) Enables acyl-CoA hydrolase activity. Involved in acyl-CoA metabolic process; long-chain fatty acid metabolic process; and very long-chain fatty acid metabolic process. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

HEATR4 (HGNC:16761): (HEAT repeat containing 4) Predicted to enable oxidoreductase activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-73537589-C-T is Benign according to our data. Variant chr14-73537589-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 778484.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.185 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 69 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037161.2. 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
	ACOT1	NM_001037161.2	MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 1 of 3	NP_001032238.1	E9KL42
	HEATR4	NM_001220484.1	MANE Select	c.-151-7345G>A		intron	N/A	NP_001207413.1	Q86WZ0
	HEATR4	NM_203309.2		c.-72-14365G>A		intron	N/A	NP_976054.2	Q86WZ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACOT1	ENST00000311148.9	TSL:1 MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 1 of 3	ENSP00000311224.4	Q86TX2
	ACOT1	ENST00000557556.1	TSL:1	c.168C>T	p.Thr56Thr	synonymous	Exon 1 of 3	ENSP00000451764.1	G3V4F2
	HEATR4	ENST00000553558.6	TSL:2 MANE Select	c.-151-7345G>A		intron	N/A	ENSP00000450444.2	Q86WZ0

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 425 AN: 116160 Hom.: 68 Cov.: 19

Gnomad AFR AF: 0.00798

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00111

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.00649

GnomAD2 exomes AF: 0.00128 AC: 162 AN: 126710 AF XY: 0.00126

Gnomad AFR exome AF: 0.00260

Gnomad AMR exome AF: 0.000409

Gnomad ASJ exome AF: 0.000330

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00181

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.00152

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000482 AC: 527 AN: 1092414 Hom.: 158 Cov.: 29 AF XY: 0.000440 AC XY: 239 AN XY: 542676

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00506 AC: 137 AN: 27076

American (AMR) AF: 0.000403 AC: 11 AN: 27312

Ashkenazi Jewish (ASJ) AF: 0.000420 AC: 8 AN: 19026

East Asian (EAS) AF: 0.00 AC: 0 AN: 10202

South Asian (SAS) AF: 0.000136 AC: 9 AN: 66158

European-Finnish (FIN) AF: 0.000490 AC: 14 AN: 28546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3166

European-Non Finnish (NFE) AF: 0.000345 AC: 299 AN: 866414

Other (OTH) AF: 0.00110 AC: 49 AN: 44514

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00367 AC: 426 AN: 116220 Hom.: 69 Cov.: 19 AF XY: 0.00369 AC XY: 207 AN XY: 56052

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00799 AC: 291 AN: 36434

American (AMR) AF: 0.00241 AC: 26 AN: 10770

Ashkenazi Jewish (ASJ) AF: 0.00111 AC: 3 AN: 2714

East Asian (EAS) AF: 0.00 AC: 0 AN: 1448

South Asian (SAS) AF: 0.00106 AC: 4 AN: 3784

European-Finnish (FIN) AF: 0.00248 AC: 17 AN: 6842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.00145 AC: 75 AN: 51866

Other (OTH) AF: 0.00640 AC: 10 AN: 1562

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00379 Hom.: 6

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.92
PhyloP100		-0.18
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism

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: rs779044350; hg19: chr14-74004293; COSMIC: COSV58575305; COSMIC: COSV58575305;