10-17613982-T-C

Variant names:

• chr10-17613982-T-C
• rs2461891
• NM_014241.4:c.257+3101A>G

Variant summary

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

The NM_014241.4(HACD1):​c.257+3101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 152,192 control chromosomes in the GnomAD database, including 51,486 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 0.82 (51486 hom., cov: 33)
• Consequence: HACD1 NM_014241.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.558
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.257+3101A>G		intron_variant	Intron 1 of 6	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.257+3101A>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.257+3101A>G		intron_variant	Intron 1 of 6	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000632169.1	n.292+3101A>G		intron_variant	Intron 1 of 1	1
HACD1	ENST00000466335.1	c.152+3101A>G		intron_variant	Intron 1 of 4	2		ENSP00000462336.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124158 AN: 152074 Hom.: 51421 Cov.: 33

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.819

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

GnomAD4 genome AF: 0.817 AC: 124286 AN: 152192 Hom.: 51486 Cov.: 33 AF XY: 0.817 AC XY: 60750 AN XY: 74390

African (AFR) AF: 0.954 AC: 39647 AN: 41550

American (AMR) AF: 0.830 AC: 12690 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2919 AN: 3468

East Asian (EAS) AF: 0.895 AC: 4624 AN: 5166

South Asian (SAS) AF: 0.791 AC: 3806 AN: 4814

European-Finnish (FIN) AF: 0.738 AC: 7811 AN: 10578

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50153 AN: 68004

Other (OTH) AF: 0.823 AC: 1736 AN: 2110

Alfa AF: 0.765 Hom.: 74468

Bravo AF: 0.831

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.55
PhyloP100		-0.56
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: rs2461891; hg19: chr10-17655981;