rs10508533

Variant names:

• chr10-17607890-A-C
• rs10508533
• NM_014241.4:c.258-3843T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-17607890-A-C
• chr10-17607890-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014241.4(HACD1):​c.258-3843T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,076 control chromosomes in the GnomAD database, including 7,042 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7042 hom., cov: 32)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.258-3843T>G		intron_variant	Intron 1 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.258-3843T>G		intron_variant	Intron 1 of 4		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.258-3843T>G		intron_variant	Intron 1 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000632169.1	n.293-3843T>G		intron_variant	Intron 1 of 1	1
HACD1	ENST00000466335.1	c.153-3843T>G		intron_variant	Intron 1 of 4	2		ENSP00000462336.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44409 AN: 151958 Hom.: 7038 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.293

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44440 AN: 152076 Hom.: 7042 Cov.: 32 AF XY: 0.285 AC XY: 21208 AN XY: 74346

African (AFR) AF: 0.378 AC: 15654 AN: 41444

American (AMR) AF: 0.226 AC: 3448 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.121 AC: 581 AN: 4816

European-Finnish (FIN) AF: 0.284 AC: 3005 AN: 10586

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19826 AN: 67986

Other (OTH) AF: 0.290 AC: 612 AN: 2110

Alfa AF: 0.286 Hom.: 19119

Bravo AF: 0.296

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.75
PhyloP100		0.95
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: rs10508533; hg19: chr10-17649889;