10-17594086-G-A

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.784+119C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 947,910 control chromosomes in the GnomAD database, including 30,319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5036 hom., cov: 32)
  • Exomes 𝑓: 0.25 (25283 hom.)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

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=-0.89).
• BP6: Variant 10-17594086-G-A is Benign according to our data. Variant chr10-17594086-G-A is described in ClinVar as [Benign]. Clinvar id is 1264544.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.784+119C>T		intron_variant		ENST00000361271.8
HACD1	XM_005252641.5	c.676+119C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD1	ENST00000361271.8	c.784+119C>T		intron_variant		1	NM_014241.4	P1
HACD1	ENST00000498812.5	c.*173+119C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38011 AN: 151858 Hom.: 5031 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.246 AC: 195618 AN: 795938 Hom.: 25283 AF XY: 0.246 AC XY: 94668 AN XY: 384616

Gnomad4 AFR exome AF: 0.223

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.0292

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.260

Gnomad4 OTH exome AF: 0.237

GnomAD4 genome AF: 0.250 AC: 38028 AN: 151972 Hom.: 5036 Cov.: 32 AF XY: 0.243 AC XY: 18088 AN XY: 74284

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.0510

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.247

Alfa AF: 0.176 Hom.: 456

Bravo AF: 0.247

Asia WGS AF: 0.120 AC: 416 AN: 3468

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.62

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: rs3817472; hg19: chr10-17636085;