10-17594248-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_014241.4(HACD1):c.741C>T(p.Asp247=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00152 in 1,592,604 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (18 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (17 hom.)
• Consequence: HACD1 NM_014241.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.93

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 10-17594248-G-A is Benign according to our data. Variant chr10-17594248-G-A is described in ClinVar as [Benign]. Clinvar id is 780851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00758 (1154/152262) while in subpopulation AFR AF= 0.0267 (1108/41562). AF 95% confidence interval is 0.0254. There are 18 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HACD1	NM_014241.4	c.741C>T	p.Asp247=	synonymous_variant	6/7	ENST00000361271.8
HACD1	XM_005252641.5	c.633C>T	p.Asp211=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HACD1	ENST00000361271.8	c.741C>T	p.Asp247=	synonymous_variant	6/7	1	NM_014241.4	P1
HACD1	ENST00000471481.1	n.527C>T		non_coding_transcript_exon_variant	3/3	3
HACD1	ENST00000498812.5	c.*130C>T		3_prime_UTR_variant, NMD_transcript_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00753 AC: 1146 AN: 152144 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00202 AC: 485 AN: 240078 Hom.: 3 AF XY: 0.00150 AC XY: 195 AN XY: 130298

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000692

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000726

Gnomad OTH exome AF: 0.000867

GnomAD4 exome AF: 0.000876 AC: 1262 AN: 1440342 Hom.: 17 Cov.: 30 AF XY: 0.000842 AC XY: 603 AN XY: 716272

Gnomad4 AFR exome AF: 0.0298

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000846

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000916

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome AF: 0.00758 AC: 1154 AN: 152262 Hom.: 18 Cov.: 33 AF XY: 0.00713 AC XY: 531 AN XY: 74452

Gnomad4 AFR AF: 0.0267

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00304 Hom.: 4

Bravo AF: 0.00817

Asia WGS AF: 0.00405 AC: 14 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

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	8.0
Dann	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs17141386; hg19: chr10-17636247;