3-15601536-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
HACL1	NM_012260.4	c.-73T>C		5_prime_UTR_variant	1/17	ENST00000321169.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACL1	ENST00000321169.10	c.-73T>C		5_prime_UTR_variant	1/17	1	NM_012260.4	P1

Frequencies

GnomAD3 genomes AF: 0.962 AC: 146394 AN: 152220 Hom.: 70452 Cov.: 32

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

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

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.: 32 AF XY: 0.962 AC XY: 71661 AN XY: 74482

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs2019160; hg19: chr3-15643043;