Variant 3-15568563-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_012260.4(HACL1):c.1119G>A(p.Leu373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,551,692 control chromosomes in the GnomAD database, including 11,164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 950 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10214 hom. )

Consequence

HACL1
NM_012260.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.09

Variant links:

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]

HACL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 3-15568563-C-T is Benign according to our data. Variant chr3-15568563-C-T is described in ClinVar as [Benign]. Clinvar id is 3057081.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACL1	NM_012260.4 linkuse as main transcript	c.1119G>A	p.Leu373=	synonymous_variant	13/17	ENST00000321169.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACL1	ENST00000321169.10 linkuse as main transcript	c.1119G>A	p.Leu373=	synonymous_variant	13/17	1	NM_012260.4	P1	Q9UJ83-1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16481

AN:

152046

Hom.:

953

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.0844

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.114

GnomAD3 exomes

AF:

0.115

AC:

26517

AN:

231572

Hom.:

1659

AF XY:

0.118

AC XY:

14758

AN XY:

125166

show subpopulations

Gnomad AFR exome

AF:

0.0799

Gnomad AMR exome

AF:

0.0485

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.118

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.117

AC:

163163

AN:

1399528

Hom.:

10214

Cov.:

AF XY:

0.118

AC XY:

82572

AN XY:

697148

show subpopulations

Gnomad4 AFR exome

AF:

0.0787

Gnomad4 AMR exome

AF:

0.0520

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.119

Gnomad4 NFE exome

AF:

0.115

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.108

AC:

16484

AN:

152164

Hom.:

950

Cov.:

AF XY:

0.110

AC XY:

8157

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0817

Gnomad4 AMR

AF:

0.0842

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.114

Hom.:

1546

Bravo

AF:

0.102

Asia WGS

AF:

0.117

AC:

404

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HACL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 15, 2024

This variant is classified as 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

-0.33

CADD

Benign

8.8

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over