chr3-123582256-T-C

Variant names:

• chr3-123582256-T-C
• rs760203086
• NM_198402.5:c.229A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198402.5(HACD2):​c.229A>G​(p.Ile77Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000348 in 1,607,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (1 hom.)
• Consequence: HACD2 NM_198402.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.72
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043421596).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198402.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD2	NM_198402.5	MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 7	NP_940684.1	Q6Y1H2
	HACD2	NM_001329783.2		c.229A>G	p.Ile77Val	missense	Exon 2 of 8	NP_001316712.1
	HACD2	NM_001329784.4		c.-242A>G		5_prime_UTR	Exon 2 of 9	NP_001316713.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HACD2	ENST00000383657.10	TSL:1 MANE Select	c.229A>G	p.Ile77Val	missense	Exon 2 of 7	ENSP00000373153.5	Q6Y1H2
	HACD2	ENST00000865300.1		c.229A>G	p.Ile77Val	missense	Exon 2 of 7	ENSP00000535359.1
	HACD2	ENST00000865299.1		c.229A>G	p.Ile77Val	missense	Exon 2 of 5	ENSP00000535358.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000898 AC: 22 AN: 245070 AF XY: 0.0000300

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000512

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000447

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 54 AN: 1455738 Hom.: 1 Cov.: 30 AF XY: 0.0000249 AC XY: 18 AN XY: 724208

African (AFR) AF: 0.00 AC: 0 AN: 33154

American (AMR) AF: 0.000387 AC: 17 AN: 43922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39360

South Asian (SAS) AF: 0.00 AC: 0 AN: 85128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.0000325 AC: 36 AN: 1109100

Other (OTH) AF: 0.00 AC: 0 AN: 60082

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000529

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000579 AC: 7

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.010
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.50	N
PhyloP100		5.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.072
Sift	Benign	0.54	T
Sift4G	Benign	0.81	T
Polyphen		0.0090	B
Vest4		0.22
MVP		0.043
MPC		0.64
ClinPred		0.078	T
GERP RS		4.6
Varity_R		0.067
gMVP		0.50
Mutation Taster		=95/5	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: rs760203086; hg19: chr3-123301103;