3-123585018-C-G

Variant names:

• chr3-123585018-C-G
• rs1185487869
• NM_198402.5:c.10G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198402.5(HACD2):​c.10G>C​(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: HACD2 NM_198402.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06429416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD2	NM_198402.5	c.10G>C	p.Val4Leu	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.10G>C	p.Val4Leu	missense_variant	Exon 1 of 7	1	NM_198402.5	ENSP00000373153.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356204 Hom.: 0 Cov.: 34 AF XY: 0.00000150 AC XY: 1 AN XY: 668088

African (AFR) AF: 0.00 AC: 0 AN: 27580

American (AMR) AF: 0.00 AC: 0 AN: 30696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23146

East Asian (EAS) AF: 0.00 AC: 0 AN: 31078

South Asian (SAS) AF: 0.00 AC: 0 AN: 74594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4696

European-Non Finnish (NFE) AF: 9.41e-7 AC: 1 AN: 1062690

Other (OTH) AF: 0.00 AC: 0 AN: 56220

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.028
Sift	Benign	0.32	T
Sift4G	Uncertain	0.051	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.22		Loss of catalytic residue at V4 (P = 0.0176);
MVP		0.043
MPC		0.65
ClinPred		0.13	T
GERP RS		2.2
PromoterAI		-0.087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.085
gMVP		0.30
Mutation Taster		=93/7	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: rs1185487869; hg19: chr3-123303865;