rs748902443

Variant names:

• chr3-123494913-G-A
• rs748902443
• NM_198402.5:c.740C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-123494913-G-A
• chr3-123494913-G-T

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.740C>T​(p.Thr247Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000284 in 1,407,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. T247N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: HACD2 NM_198402.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.78
• 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]

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=0.118631124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD2	NM_198402.5	c.740C>T	p.Thr247Ile	missense_variant	Exon 7 of 7	ENST00000383657.10	NP_940684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD2	ENST00000383657.10	c.740C>T	p.Thr247Ile	missense_variant	Exon 7 of 7	1	NM_198402.5	ENSP00000373153.5
HACD2	ENST00000471236.1	n.-83C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1407124 Hom.: 0 Cov.: 28 AF XY: 0.00000144 AC XY: 1 AN XY: 694930

African (AFR) AF: 0.00 AC: 0 AN: 32108

American (AMR) AF: 0.00 AC: 0 AN: 36822

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25214

East Asian (EAS) AF: 0.00 AC: 0 AN: 37158

South Asian (SAS) AF: 0.00 AC: 0 AN: 79564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000370 AC: 4 AN: 1082076

Other (OTH) AF: 0.00 AC: 0 AN: 58388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	0.025
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.8
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.16	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.47		Gain of helix (P = 0.027);
MVP		0.043
MPC		0.72
ClinPred		0.58	D
GERP RS		6.1
Varity_R		0.083
gMVP		0.33
Mutation Taster		=70/30	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: rs748902443; hg19: chr3-123213760;