Variant rs2294851 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018194.6(HHAT):c.545G>A(p.Ser182Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,550 control chromosomes in the GnomAD database, including 18,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1301 hom., cov: 32)

Exomes 𝑓: 0.15 ( 16716 hom. )

Consequence

HHAT
NM_018194.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 8.99

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021119118).

BP6

Variant 1-210404540-G-A is Benign according to our data. Variant chr1-210404540-G-A is described in ClinVar as [Benign]. Clinvar id is 1587713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHAT	NM_018194.6 linkuse as main transcript	c.545G>A	p.Ser182Asn	missense_variant	6/12	ENST00000261458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHAT	ENST00000261458.8 linkuse as main transcript	c.545G>A	p.Ser182Asn	missense_variant	6/12	2	NM_018194.6	P1	Q5VTY9-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17526

AN:

152146

Hom.:

1298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0293

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.259

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.149

AC:

37569

AN:

251358

Hom.:

3218

AF XY:

0.146

AC XY:

19775

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0242

Gnomad AMR exome

AF:

0.219

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.275

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.132

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.147

AC:

214164

AN:

1461286

Hom.:

16716

Cov.:

AF XY:

0.145

AC XY:

105434

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.0211

Gnomad4 AMR exome

AF:

0.210

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.115

AC:

17525

AN:

152264

Hom.:

1301

Cov.:

AF XY:

0.117

AC XY:

8690

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.259

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.137

Hom.:

2322

Bravo

AF:

0.116

TwinsUK

AF:

0.155

AC:

574

ALSPAC

AF:

0.152

AC:

585

ESP6500AA

AF:

0.0295

AC:

130

ESP6500EA

AF:

0.143

AC:

1231

ExAC

AF:

0.144

AC:

17471

Asia WGS

AF:

0.173

AC:

600

AN:

3478

EpiCase

AF:

0.137

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;.;.;D;D;.

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.64

T;T;T;.;.;T

MetaRNN

Benign

0.0021

T;T;T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.0

M;.;.;M;M;.

MutationTaster

Benign

1.1e-7

P;P;P;P;P;P;P;P;P

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

N;N;N;N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.015

D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

1.0

D;.;.;D;D;.

Vest4

0.47

MPC

0.51

ClinPred

0.019

GERP RS

5.5

Varity_R

0.60

gMVP

0.89

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over