chr3-123585018-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001329784.4(HACD2):​c.-461G>A 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07161051).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD2	NM_198402.5	c.10G>A	p.Val4Met	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>A	p.Val4Met	missense_variant	Exon 1 of 7	1	NM_198402.5	ENSP00000373153.5
MYLK-AS1	ENST00000703248.1	n.-125C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1356204 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 668088

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.0	N
REVEL	Benign	0.027
Sift	Benign	0.23	T
Sift4G	Uncertain	0.020	D
Polyphen		0.0	B
Vest4		0.093
MutPred		0.27		Gain of MoRF binding (P = 0.1287);
MVP		0.043
MPC		0.66
ClinPred		0.13	T
GERP RS		2.2
Varity_R		0.069
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1185487869; hg19: chr3-123303865;