Variant chr3-123567768-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_198402.5(HACD2):c.286G>T(p.Ala96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000032 in 1,498,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

HACD2
NM_198402.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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:

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
HACD2	NM_198402.5 linkuse as main transcript	c.286G>T	p.Ala96Ser	missense_variant	3/7	ENST00000383657.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD2	ENST00000383657.10 linkuse as main transcript	c.286G>T	p.Ala96Ser	missense_variant	3/7	1	NM_198402.5	P1
HACD2	ENST00000469317.1 linkuse as main transcript	c.-10G>T		5_prime_UTR_variant	3/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000154

AC:

AN:

194312

Hom.:

AF XY:

0.0000280

AC XY:

AN XY:

107326

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:

0.0000312

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000327

AC:

AN:

1346888

Hom.:

Cov.:

AF XY:

0.0000432

AC XY:

AN XY:

671844

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:

0.0000411

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151966

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000908

Hom.:

ExAC

AF:

0.0000249

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 25, 2022

The c.286G>T (p.A96S) alteration is located in exon 3 (coding exon 3) of the HACD2 gene. This alteration results from a G to T substitution at nucleotide position 286, causing the alanine (A) at amino acid position 96 to be replaced by a serine (S). 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

0.29

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.41

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.0

REVEL

Benign

0.18

Sift

Benign

0.057

Sift4G

Benign

0.085

Polyphen

0.80

Vest4

0.61

MutPred

0.67

Gain of sheet (P = 0.1208);

MVP

0.18

MPC

1.2

ClinPred

0.58

GERP RS

4.6

Varity_R

0.21

gMVP

0.56

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