3-123585011-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198402.5(HACD2):​c.17C>T​(p.Ala6Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000525 in 1,505,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HACD2
NM_198402.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.43

Publications

0 publications found
Variant links:
Genes affected
HACD2 (HGNC:9640): (3-hydroxyacyl-CoA dehydratase 2) The protein encoded by this gene can catalyze the third step (dehydration) in the conversion of long chain fatty acids to very long chain fatty acids. The encoded protein localizes to the endoplasmic reticulum membrane. [provided by RefSeq, Jul 2016]
MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005436361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HACD2NM_198402.5 linkc.17C>T p.Ala6Val missense_variant Exon 1 of 7 ENST00000383657.10 NP_940684.1 Q6Y1H2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HACD2ENST00000383657.10 linkc.17C>T p.Ala6Val missense_variant Exon 1 of 7 1 NM_198402.5 ENSP00000373153.5 Q6Y1H2

Frequencies

GnomAD3 genomes
AF:
0.000309
AC:
47
AN:
152216
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000392
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000927
AC:
9
AN:
97040
AF XY:
0.000111
show subpopulations
Gnomad AFR exome
AF:
0.000469
Gnomad AMR exome
AF:
0.000273
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000203
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000596
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000177
AC:
24
AN:
1352680
Hom.:
0
Cov.:
34
AF XY:
0.0000165
AC XY:
11
AN XY:
666222
show subpopulations
African (AFR)
AF:
0.000436
AC:
12
AN:
27532
American (AMR)
AF:
0.000197
AC:
6
AN:
30472
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22962
East Asian (EAS)
AF:
0.0000646
AC:
2
AN:
30982
South Asian (SAS)
AF:
0.00
AC:
0
AN:
74452
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
45042
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4612
European-Non Finnish (NFE)
AF:
0.00000189
AC:
2
AN:
1060594
Other (OTH)
AF:
0.0000357
AC:
2
AN:
56032
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000361
AC:
55
AN:
152334
Hom.:
0
Cov.:
34
AF XY:
0.000443
AC XY:
33
AN XY:
74504
show subpopulations
African (AFR)
AF:
0.00118
AC:
49
AN:
41592
American (AMR)
AF:
0.000392
AC:
6
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5170
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
2
4
7
9
11
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000356
Hom.:
0
Bravo
AF:
0.000310
ExAC
AF:
0.0000740
AC:
7
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 12, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.17C>T (p.A6V) alteration is located in exon 1 (coding exon 1) of the HACD2 gene. This alteration results from a C to T substitution at nucleotide position 17, causing the alanine (A) at amino acid position 6 to be replaced by a valine (V). 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
0.28
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0073
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.34
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.50
T
M_CAP
Uncertain
0.090
D
MetaRNN
Benign
0.0054
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N
PhyloP100
5.4
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.42
N
REVEL
Benign
0.029
Sift
Uncertain
0.013
D
Sift4G
Benign
0.55
T
Polyphen
0.063
B
Vest4
0.15
MutPred
0.29
Gain of catalytic residue at A6 (P = 0.0175);
MVP
0.043
MPC
0.66
ClinPred
0.18
T
GERP RS
2.7
PromoterAI
-0.030
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7
Varity_R
0.13
gMVP
0.42
Mutation Taster
=94/6
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs563998127; hg19: chr3-123303858; API