NM_014241.4:c.606-130G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014241.4(HACD1):​c.606-130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 670,310 control chromosomes in the GnomAD database, including 20,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4853 hom., cov: 32)
  • Exomes 𝑓: 0.24 (15821 hom.)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0120
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-17594513-C-T is Benign according to our data. Variant chr10-17594513-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.606-130G>A		intron_variant	Intron 5 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.498-130G>A		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>A		intron_variant	Intron 5 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000471481.1	n.392-130G>A		intron_variant	Intron 2 of 2	3
HACD1	ENST00000498812.5	n.109-130G>A		intron_variant	Intron 2 of 3	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37278 AN: 151914 Hom.: 4848 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.0509

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.235 AC: 121884 AN: 518278 Hom.: 15821 AF XY: 0.236 AC XY: 60605 AN XY: 256640

African (AFR) AF: 0.207 AC: 2665 AN: 12902

American (AMR) AF: 0.147 AC: 1482 AN: 10096

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 3495 AN: 11210

East Asian (EAS) AF: 0.0275 AC: 727 AN: 26482

South Asian (SAS) AF: 0.127 AC: 1552 AN: 12258

European-Finnish (FIN) AF: 0.232 AC: 7658 AN: 33032

Middle Eastern (MID) AF: 0.238 AC: 440 AN: 1846

European-Non Finnish (NFE) AF: 0.255 AC: 98051 AN: 385260

Other (OTH) AF: 0.231 AC: 5814 AN: 25192

GnomAD4 genome AF: 0.245 AC: 37292 AN: 152032 Hom.: 4853 Cov.: 32 AF XY: 0.239 AC XY: 17739 AN XY: 74330

African (AFR) AF: 0.230 AC: 9527 AN: 41472

American (AMR) AF: 0.187 AC: 2851 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3468

East Asian (EAS) AF: 0.0509 AC: 264 AN: 5190

South Asian (SAS) AF: 0.167 AC: 806 AN: 4816

European-Finnish (FIN) AF: 0.238 AC: 2503 AN: 10532

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19254 AN: 67958

Other (OTH) AF: 0.245 AC: 515 AN: 2104

Alfa AF: 0.255 Hom.: 649

Bravo AF: 0.241

Asia WGS AF: 0.120 AC: 417 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.0
DANN	Benign	0.40
PhyloP100		-0.012
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: rs11599234; hg19: chr10-17636512;