Variant chr3-15601536-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012260.4(HACL1):c.-73T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.954 in 1,606,886 control chromosomes in the GnomAD database, including 731,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 70512 hom., cov: 32)

Exomes 𝑓: 0.95 ( 660996 hom. )

Consequence

HACL1
NM_012260.4 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.05

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:

BTD (HGNC:1122): (biotinidase) The protein encoded by this gene functions to recycle protein-bound biotin by cleaving biocytin (biotin-epsilon-lysine), a normal product of carboxylase degradation, resulting in regeneration of free biotin. The encoded protein has also been shown to have biotinyl transferase activity. Mutations in this gene are associated with biotinidase deficiency. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Aug 2013]

BTD links:

HACL1 (HGNC:):

HACL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-15601536-A-G is Benign according to our data. Variant chr3-15601536-A-G is described in ClinVar as [Benign]. Clinvar id is 1266847.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15601536-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HACL1	NM_012260.4 linkuse as main transcript	c.-73T>C		5_prime_UTR_variant	1/17	ENST00000321169.10	NP_036392.2	Q9UJ83-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HACL1	ENST00000321169.10 linkuse as main transcript	c.-73T>C		5_prime_UTR_variant	1/17	1	NM_012260.4	ENSP00000323811.5		Q9UJ83-1

Frequencies

GnomAD3 genomes

AF:

0.962

AC:

146394

AN:

152220

Hom.:

70452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.992

Gnomad AMI

AF:

0.889

Gnomad AMR

AF:

0.960

Gnomad ASJ

AF:

0.948

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.959

Gnomad NFE

AF:

0.949

Gnomad OTH

AF:

0.953

GnomAD3 exomes

AF:

0.958

AC:

235112

AN:

245494

Hom.:

112645

AF XY:

0.956

AC XY:

127322

AN XY:

133210

show subpopulations

Gnomad AFR exome

AF:

0.991

Gnomad AMR exome

AF:

0.969

Gnomad ASJ exome

AF:

0.946

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.960

Gnomad FIN exome

AF:

0.927

Gnomad NFE exome

AF:

0.948

Gnomad OTH exome

AF:

0.949

GnomAD4 exome

AF:

0.953

AC:

1386505

AN:

1454548

Hom.:

660996

Cov.:

128

AF XY:

0.953

AC XY:

689871

AN XY:

723922

show subpopulations

Gnomad4 AFR exome

AF:

0.993

Gnomad4 AMR exome

AF:

0.969

Gnomad4 ASJ exome

AF:

0.944

Gnomad4 EAS exome

AF:

0.994

Gnomad4 SAS exome

AF:

0.960

Gnomad4 FIN exome

AF:

0.925

Gnomad4 NFE exome

AF:

0.951

Gnomad4 OTH exome

AF:

0.956

GnomAD4 genome

AF:

0.962

AC:

146514

AN:

152338

Hom.:

70512

Cov.:

AF XY:

0.962

AC XY:

71661

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.992

Gnomad4 AMR

AF:

0.960

Gnomad4 ASJ

AF:

0.948

Gnomad4 EAS

AF:

0.994

Gnomad4 SAS

AF:

0.962

Gnomad4 FIN

AF:

0.927

Gnomad4 NFE

AF:

0.949

Gnomad4 OTH

AF:

0.954

Alfa

AF:

0.959

Hom.:

14357

Bravo

AF:

0.965

Asia WGS

AF:

0.970

AC:

3375

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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