rs11599234

chr10-17594513-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -0.0120

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1262369.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	UniProt
HACD1	NM_014241.4	c.606-130G>A		intron_variant		ENST00000361271.8
HACD1	XM_005252641.5	c.498-130G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD1	ENST00000361271.8	c.606-130G>A		intron_variant		1	NM_014241.4	P1
HACD1	ENST00000498812.5	c.109-130G>A		intron_variant, NMD_transcript_variant		5
HACD1	ENST00000471481.1	n.392-130G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.0275

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.255

Gnomad4 OTH exome AF: 0.231

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

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.0509

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.245

Alfa AF: 0.256 Hom.: 628

Bravo AF: 0.241

Asia WGS AF: 0.120 AC: 417 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.0
Dann	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs11599234; hg19: chr10-17636512;