3-15567937-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012260.4(HACL1):ā€‹c.1316T>Cā€‹(p.Val439Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

HACL1
NM_012260.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HACL1NM_012260.4 linkuse as main transcriptc.1316T>C p.Val439Ala missense_variant 14/17 ENST00000321169.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HACL1ENST00000321169.10 linkuse as main transcriptc.1316T>C p.Val439Ala missense_variant 14/171 NM_012260.4 P1Q9UJ83-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251376
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135854
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461606
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000468
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 14, 2024The c.1316T>C (p.V439A) alteration is located in exon 14 (coding exon 14) of the HACL1 gene. This alteration results from a T to C substitution at nucleotide position 1316, causing the valine (V) at amino acid position 439 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.067
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
22
DANN
Benign
0.86
DEOGEN2
Benign
0.25
T;.;.;.;.
Eigen
Benign
0.11
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
D;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Uncertain
0.50
D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.45
N;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.4
N;N;N;N;N
REVEL
Benign
0.17
Sift
Benign
0.54
T;T;T;T;T
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
0.74
P;P;.;.;.
Vest4
0.57
MutPred
0.47
Gain of disorder (P = 0.0487);.;.;.;.;
MVP
0.42
MPC
0.11
ClinPred
0.40
T
GERP RS
5.7
Varity_R
0.081
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs1559547789; hg19: chr3-15609444; API