chr3-123585020-G-T

Variant names:

• chr3-123585020-G-T
• rs1034065745
• NM_198402.5:c.8C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198402.5(HACD2):​c.8C>A​(p.Ala3Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,350,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: HACD2 NM_198402.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 publications found

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)

ACMG classification

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=0.14143202).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD2	NM_198402.5	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 7	ENST00000383657.10	NP_940684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD2	ENST00000383657.10	c.8C>A	p.Ala3Glu	missense_variant	Exon 1 of 7	1	NM_198402.5	ENSP00000373153.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000296 AC: 4 AN: 1350626 Hom.: 0 Cov.: 34 AF XY: 0.00000301 AC XY: 2 AN XY: 665266

African (AFR) AF: 0.00 AC: 0 AN: 27434

American (AMR) AF: 0.00 AC: 0 AN: 30194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22902

East Asian (EAS) AF: 0.00 AC: 0 AN: 30844

South Asian (SAS) AF: 0.0000539 AC: 4 AN: 74266

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1059358

Other (OTH) AF: 0.00 AC: 0 AN: 55898

GnomAD4 genome Cov.: 34

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.069
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.018	D
Polyphen		0.67	P
Vest4		0.16
MutPred		0.25		Gain of solvent accessibility (P = 0.0145);
MVP		0.043
MPC		0.77
ClinPred		0.58	D
GERP RS		3.6
PromoterAI		0.33	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.30
gMVP		0.80
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

Other links and lift over

dbSNP: rs1034065745; hg19: chr3-123303867;