dbSNP rs541937721: HACD1:p.His279Gln (chr10-17590394-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014241.4(HACD1):c.837T>G(p.His279Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

HACD1
NM_014241.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16901323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4 link	c.837T>G	p.His279Gln	missense_variant	Exon 7 of 7	ENST00000361271.8	NP_055056.3	B0YJ81-1
HACD1	XM_005252641.5 link	c.729T>G	p.His243Gln	missense_variant	Exon 5 of 5		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HACD1	ENST00000361271.8 link	c.837T>G	p.His279Gln	missense_variant	Exon 7 of 7	1	NM_014241.4	ENSP00000355308.3	B0YJ81-1
HACD1	ENST00000498812.5 link	n.*226T>G		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000462868.1	J3KT94
HACD1	ENST00000498812.5 link	n.*226T>G		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000462868.1	J3KT94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452476

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

M_CAP

Benign

0.0096

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.64

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.095

Sift4G

Benign

0.10

Polyphen

0.0060

Vest4

0.41

MutPred

0.50

Loss of catalytic residue at L278 (P = 0.1455);

MVP

0.14

MPC

0.77

ClinPred

0.90

GERP RS

-4.0

Varity_R

0.36

gMVP

0.60

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over