rs2357285

chr10-17590563-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.785-117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 637,922 control chromosomes in the GnomAD database, including 879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (155 hom., cov: 32)
  • Exomes 𝑓: 0.048 (724 hom.)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.58

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=-0.87).
• BP6: Variant 10-17590563-C-T is Benign according to our data. Variant chr10-17590563-C-T is described in ClinVar as [Benign]. Clinvar id is 1264618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0601 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACD1	NM_014241.4	c.785-117G>A		intron_variant		ENST00000361271.8
HACD1	XM_005252641.5	c.677-117G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD1	ENST00000361271.8	c.785-117G>A		intron_variant		1	NM_014241.4	P1
HACD1	ENST00000498812.5	c.*174-117G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5880 AN: 152100 Hom.: 155 Cov.: 32

Gnomad AFR AF: 0.0101

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0152

Gnomad FIN AF: 0.0464

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0616

Gnomad OTH AF: 0.0297

GnomAD4 exome AF: 0.0477 AC: 23157 AN: 485704 Hom.: 724 AF XY: 0.0470 AC XY: 12062 AN XY: 256616

Gnomad4 AFR exome AF: 0.00808

Gnomad4 AMR exome AF: 0.0150

Gnomad4 ASJ exome AF: 0.0384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0148

Gnomad4 FIN exome AF: 0.0515

Gnomad4 NFE exome AF: 0.0592

Gnomad4 OTH exome AF: 0.0416

GnomAD4 genome AF: 0.0387 AC: 5885 AN: 152218 Hom.: 155 Cov.: 32 AF XY: 0.0369 AC XY: 2743 AN XY: 74408

Gnomad4 AFR AF: 0.0101

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0158

Gnomad4 FIN AF: 0.0464

Gnomad4 NFE AF: 0.0617

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0511 Hom.: 256

Bravo AF: 0.0353

Asia WGS AF: 0.00722 AC: 26 AN: 3478

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	-0.87
Cadd	Benign	5.0
Dann	Benign	0.68

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: rs2357285; hg19: chr10-17632562;