NM_014241.4:c.484-715T>C

Variant names:

• chr10-17600126-A-G
• rs7073625
• NM_014241.4:c.484-715T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014241.4(HACD1):​c.484-715T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,044 control chromosomes in the GnomAD database, including 10,025 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 0.35 (10025 hom., cov: 32)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.484-715T>C		intron_variant	Intron 4 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.376-715T>C		intron_variant	Intron 2 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.484-715T>C		intron_variant	Intron 4 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000466335.1	c.379-715T>C		intron_variant	Intron 4 of 4	2		ENSP00000462336.1
HACD1	ENST00000471481.1	n.270-715T>C		intron_variant	Intron 1 of 2	3
HACD1	ENST00000498812.5	n.108+3434T>C		intron_variant	Intron 2 of 3	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53819 AN: 151924 Hom.: 10023 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.354 AC: 53839 AN: 152044 Hom.: 10025 Cov.: 32 AF XY: 0.346 AC XY: 25717 AN XY: 74320

African (AFR) AF: 0.407 AC: 16875 AN: 41454

American (AMR) AF: 0.293 AC: 4477 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3462

East Asian (EAS) AF: 0.0483 AC: 250 AN: 5172

South Asian (SAS) AF: 0.202 AC: 971 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10572

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25125 AN: 67986

Other (OTH) AF: 0.377 AC: 797 AN: 2114

Alfa AF: 0.338 Hom.: 3096

Bravo AF: 0.358

Asia WGS AF: 0.152 AC: 530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.60
PhyloP100		0.020
Mutation Taster		=100/0	polymorphism (auto)

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: rs7073625; hg19: chr10-17642125;