Genetic Variant HACD2:p.Gly18Cys (chr3-123584976-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001329784.4(HACD2):c.-419G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HACD2
NM_001329784.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.196

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]

HACD2 links:

MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

MYLK-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10510507).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329784.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HACD2	NM_198402.5	MANE Select	c.52G>T	p.Gly18Cys	missense	Exon 1 of 7	NP_940684.1	Q6Y1H2
HACD2	NM_001329784.4		c.-419G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001316713.2
HACD2	NM_001329786.2		c.-263G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001316715.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HACD2	ENST00000383657.10	TSL:1 MANE Select	c.52G>T	p.Gly18Cys	missense	Exon 1 of 7	ENSP00000373153.5	Q6Y1H2
HACD2	ENST00000865300.1		c.52G>T	p.Gly18Cys	missense	Exon 1 of 7	ENSP00000535359.1
HACD2	ENST00000865299.1		c.52G>T	p.Gly18Cys	missense	Exon 1 of 5	ENSP00000535358.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1373110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676992

African (AFR)

AF:

0.00

AC:

AN:

28258

American (AMR)

AF:

0.00

AC:

AN:

33270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24234

East Asian (EAS)

AF:

0.00

AC:

AN:

31790

South Asian (SAS)

AF:

0.00

AC:

AN:

77056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4928

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1069178

Other (OTH)

AF:

0.00

AC:

AN:

56976

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000315

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.014

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.0049

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.20

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.58

REVEL

Benign

0.053

Sift

Benign

0.058

Sift4G

Uncertain

0.012

Polyphen

0.0

Vest4

0.27

MutPred

0.38

Loss of methylation at R19 (P = 0.0725)

MVP

0.043

MPC

0.70

ClinPred

0.23

GERP RS

1.0

PromoterAI

0.0041

Neutral

(source)

Varity_R

0.16

gMVP

0.69

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over