10-17594513-C-A

Variant names:

• chr10-17594513-C-A
• rs11599234
• NM_014241.4:c.606-130G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014241.4(HACD1):​c.606-130G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000192 in 520,384 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.606-130G>T		intron_variant	Intron 5 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.498-130G>T		intron_variant	Intron 3 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.606-130G>T		intron_variant	Intron 5 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000471481.1	n.392-130G>T		intron_variant	Intron 2 of 2	3
HACD1	ENST00000498812.5	n.109-130G>T		intron_variant	Intron 2 of 3	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000192 AC: 1 AN: 520384 Hom.: 0 AF XY: 0.00000388 AC XY: 1 AN XY: 257620

African (AFR) AF: 0.00 AC: 0 AN: 12972

American (AMR) AF: 0.00 AC: 0 AN: 10116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11272

East Asian (EAS) AF: 0.00 AC: 0 AN: 26492

South Asian (SAS) AF: 0.00 AC: 0 AN: 12294

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1848

European-Non Finnish (NFE) AF: 0.00000258 AC: 1 AN: 386984

Other (OTH) AF: 0.00 AC: 0 AN: 25284

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.30
PhyloP100		-0.012

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: rs11599234; hg19: chr10-17636512;