dbSNP rs606231257: HACD1:p.Tyr248Tyr (chr10-17594245-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014241.4(HACD1):c.744C>T(p.Tyr248Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000139 in 1,435,586 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

HACD1
NM_014241.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.98

Publications

0 publications found

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 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

HACD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HACD1	NM_014241.4 link	c.744C>T	p.Tyr248Tyr	synonymous_variant	Exon 6 of 7	ENST00000361271.8	NP_055056.3
HACD1	XM_005252641.5 link	c.636C>T	p.Tyr212Tyr	synonymous_variant	Exon 4 of 5		XP_005252698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
HACD1	ENST00000361271.8 link	c.744C>T	p.Tyr248Tyr	synonymous_variant	Exon 6 of 7	1	NM_014241.4	ENSP00000355308.3
HACD1	ENST00000471481.1 link	n.530C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
HACD1	ENST00000498812.5 link	n.*133C>T		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000462868.1
HACD1	ENST00000498812.5 link	n.*133C>T		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000462868.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1435586

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32206

American (AMR)

AF:

0.00

AC:

AN:

39764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24820

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.00

AC:

AN:

81942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1099942

Other (OTH)

AF:

0.00

AC:

AN:

59204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.2

(source)

DANN

Benign

0.48

PhyloP100

5.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over