rs782263866

Variant names:

• chr10-17590431-T-A
• NM_014241.4:c.800A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-17590431-T-A
• chr10-17590431-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014241.4(HACD1):​c.800A>T​(p.Tyr267Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HACD1 NM_014241.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.71

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4	c.800A>T	p.Tyr267Phe	missense_variant	Exon 7 of 7	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5	c.692A>T	p.Tyr231Phe	missense_variant	Exon 5 of 5		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HACD1	ENST00000361271.8	c.800A>T	p.Tyr267Phe	missense_variant	Exon 7 of 7	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000498812.5	n.*189A>T		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000462868.1
HACD1	ENST00000498812.5	n.*189A>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.0039	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0092	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Benign	0.057	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.33	B
Vest4		0.45
MutPred		0.89		Gain of catalytic residue at M270 (P = 0.0874);
MVP		0.37
MPC		0.28
ClinPred		0.95	D
GERP RS		5.4
Varity_R		0.44
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-17632430;