Genetic Variant HACD1:c.258-3843T>G (chr10-17607890-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014241.4(HACD1):c.258-3843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,076 control chromosomes in the GnomAD database, including 7,042 homozygotes. 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: 𝑓 0.29 ( 7042 hom., cov: 32)

Consequence

HACD1
NM_014241.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.946

Publications

5 publications found

Variant links:

Genes affected

HACD1 (HGNC:9639): (3-hydroxyacyl-CoA dehydratase 1) The protein encoded by this gene contains a characteristic catalytic motif of the protein tyrosine phosphatases (PTPs) family. The PTP motif of this protein has the highly conserved arginine residue replaced by a proline residue; thus it may represent a distinct class of PTPs. Members of the PTP family are known to be signaling molecules that regulate a variety of cellular processes. This gene was preferentially expressed in both adult and fetal heart. A much lower expression level was detected in skeletal and smooth muscle tissues, and no expression was observed in other tissues. The tissue specific expression in the developing and adult heart suggests a role in regulating cardiac development and differentiation. [provided by RefSeq, Jul 2008]

HACD1 Gene-Disease associations (from GenCC):

congenital myopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
congenital myopathy 11
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
congenital fiber-type disproportion myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

HACD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4 link	c.258-3843T>G		intron_variant	Intron 1 of 6	ENST00000361271.8	NP_055056.3	B0YJ81-1
HACD1	XM_005252641.5 link	c.258-3843T>G		intron_variant	Intron 1 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HACD1	ENST00000361271.8 link	c.258-3843T>G	intron_variant	Intron 1 of 6	1	NM_014241.4	ENSP00000355308.3	B0YJ81-1
HACD1	ENST00000632169.1 link	n.293-3843T>G	intron_variant	Intron 1 of 1	1
HACD1	ENST00000466335.1 link	c.153-3843T>G	intron_variant	Intron 1 of 4	2		ENSP00000462336.1	J3KS69

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44409

AN:

151958

Hom.:

7038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.292

AC:

44440

AN:

152076

Hom.:

7042

Cov.:

AF XY:

0.285

AC XY:

21208

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.378

AC:

15654

AN:

41444

American (AMR)

AF:

0.226

AC:

3448

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3468

East Asian (EAS)

AF:

0.00154

AC:

AN:

5184

South Asian (SAS)

AF:

0.121

AC:

581

AN:

4816

European-Finnish (FIN)

AF:

0.284

AC:

3005

AN:

10586

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19826

AN:

67986

Other (OTH)

AF:

0.290

AC:

612

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1583

3167

4750

6334

7917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.286

Hom.:

19119

Bravo

AF:

0.296

Asia WGS

AF:

0.0740

AC:

258

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.8

(source)

DANN

Benign

0.75

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over