3-15560857-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012260.4(HACL1):c.*8C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00221 in 1,593,954 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: HACL1 NM_012260.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0110

Genes affected

HACL1 (HGNC:17856): (2-hydroxyacyl-CoA lyase 1) Enables several functions, including 2-hydroxy-3-methylhexadecanoyl-CoA lyase activity; ATP binding activity; and cation binding activity. Involved in fatty acid alpha-oxidation; phytanic acid metabolic process; and protein targeting to peroxisome. Located in nucleoplasm and peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-15560857-G-A is Benign according to our data. Variant chr3-15560857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3038227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACL1	NM_012260.4	c.*8C>T		3_prime_UTR_variant	17/17	ENST00000321169.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACL1	ENST00000321169.10	c.*8C>T		3_prime_UTR_variant	17/17	1	NM_012260.4	P1

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00293

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00184 AC: 453 AN: 245940 Hom.: 2 AF XY: 0.00196 AC XY: 260 AN XY: 132950

Gnomad AFR exome AF: 0.000869

Gnomad AMR exome AF: 0.000611

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.0000552

Gnomad SAS exome AF: 0.00157

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00284

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00224 AC: 3233 AN: 1441690 Hom.: 7 Cov.: 26 AF XY: 0.00222 AC XY: 1595 AN XY: 718038

Gnomad4 AFR exome AF: 0.000853

Gnomad4 AMR exome AF: 0.000652

Gnomad4 ASJ exome AF: 0.0000771

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00164

Gnomad4 FIN exome AF: 0.00262

Gnomad4 NFE exome AF: 0.00254

Gnomad4 OTH exome AF: 0.00179

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.00180 AC XY: 134 AN XY: 74450

Gnomad4 AFR AF: 0.000674

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00291

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00228 Hom.: 0

Bravo AF: 0.00156

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HACL1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.7
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs141479215; hg19: chr3-15602364; COSMIC: COSV100337225; COSMIC: COSV100337225;