dbSNP rs1346604226: HHAT:c.-94C>A (chr1-210329054-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170587.3(HHAT):c.44C>A(p.Thr15Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000628 in 1,432,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

HHAT
NM_001170587.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.889

Publications

0 publications found

Variant links:

Genes affected

HHAT (HGNC:18270): (hedgehog acyltransferase) 'Skinny hedgehog' (SKI1) encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of 'hedgehog' (see MIM 600725).[supplied by OMIM, Jul 2002]

HHAT Gene-Disease associations (from GenCC):

chondrodysplasia-pseudohermaphroditism syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

HHAT links:

ENSG00000310145 (HGNC:):

ENSG00000310145 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07344678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170587.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HHAT	NM_018194.6	MANE Select	c.-94C>A		5_prime_UTR	Exon 1 of 12	NP_060664.2	Q5VTY9-1
HHAT	NM_001170587.3		c.44C>A	p.Thr15Asn	missense	Exon 1 of 11	NP_001164058.1	Q5VTY9-7
HHAT	NM_001170588.3		c.-94C>A		5_prime_UTR	Exon 1 of 11	NP_001164059.1	Q5VTY9-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HHAT	ENST00000261458.8	TSL:2 MANE Select	c.-94C>A		5_prime_UTR	Exon 1 of 12	ENSP00000261458.3	Q5VTY9-1
HHAT	ENST00000545154.5	TSL:2	c.44C>A	p.Thr15Asn	missense	Exon 1 of 11	ENSP00000438468.1	Q5VTY9-7
HHAT	ENST00000537898.5	TSL:2	c.-94C>A		5_prime_UTR	Exon 1 of 11	ENSP00000442625.1	Q5VTY9-5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000469

AC:

AN:

1280532

Hom.:

Cov.:

AF XY:

0.00000318

AC XY:

AN XY:

627966

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26040

American (AMR)

AF:

0.00

AC:

AN:

21574

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22246

East Asian (EAS)

AF:

0.00

AC:

AN:

27962

South Asian (SAS)

AF:

0.00

AC:

AN:

65368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32530

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.00000487

AC:

AN:

1026584

Other (OTH)

AF:

0.00

AC:

AN:

52898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68038

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.6

(source)

DANN

Benign

0.95

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.31

M_CAP

Benign

0.0049

MetaRNN

Benign

0.073

MetaSVM

Benign

-0.97

PhyloP100

-0.89

PROVEAN

Benign

-0.97

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.28

MutPred

0.16

Loss of phosphorylation at T15 (P = 0.0134)

MVP

0.030

MPC

0.12

ClinPred

0.20

GERP RS

-5.8

PromoterAI

0.26

Neutral

(source)

gMVP

0.49

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over