11-108121621-G-T

Variant names:

• chr11-108121621-G-T
• rs886047594
• NM_000019.4:c.15G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001386685.1(ACAT1):​c.-350G>T variant causes a 5 prime UTR premature start codon gain 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACAT1 NM_001386685.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147
• Publications: 0 publications found

Genes affected

ACAT1 (HGNC:93): (acetyl-CoA acetyltransferase 1) This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. Defects in this gene are associated with 3-ketothiolase deficiency, an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and butanone. [provided by RefSeq, Feb 2009]

ACAT1 Gene-Disease associations (from GenCC):

• beta-ketothiolase deficiency

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

ENSG00000255467 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 11-108121621-G-T is Benign according to our data. Variant chr11-108121621-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2180015.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386685.1. 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
	ACAT1	NM_000019.4	MANE Select	c.15G>T	p.Ala5Ala	synonymous	Exon 1 of 12	NP_000010.1	P24752-1
	ACAT1	NM_001386685.1		c.-350G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001373614.1	A0A5F9ZHJ0
	ACAT1	NM_001386686.1		c.-355G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001373615.1	A0A5F9ZHJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACAT1	ENST00000265838.9	TSL:1 MANE Select	c.15G>T	p.Ala5Ala	synonymous	Exon 1 of 12	ENSP00000265838.4	P24752-1
	ACAT1	ENST00000299355.10	TSL:1	c.15G>T	p.Ala5Ala	synonymous	Exon 1 of 6	ENSP00000299355.6	P24752-2
	ACAT1	ENST00000531813.5	TSL:1	n.15G>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000435965.1	E9PRQ6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 150684 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1398556 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 689998

African (AFR) AF: 0.00 AC: 0 AN: 31676

American (AMR) AF: 0.00 AC: 0 AN: 35828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25170

East Asian (EAS) AF: 0.00 AC: 0 AN: 35884

South Asian (SAS) AF: 0.00 AC: 0 AN: 79280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5252

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079486

Other (OTH) AF: 0.00 AC: 0 AN: 57976

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of acetyl-CoA acetyltransferase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		0.15
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs886047594; hg19: chr11-107992348;