Variant chr1-210349043-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018194.6(HHAT):c.68A>G(p.Tyr23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,614,028 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

HHAT
NM_018194.6 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.30

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014554501).

BP6

Variant 1-210349043-A-G is Benign according to our data. Variant chr1-210349043-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 775660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HHAT	NM_018194.6 link	c.68A>G	p.Tyr23Cys	missense_variant	2/12	ENST00000261458.8	NP_060664.2	Q5VTY9-1B7Z5N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8 link	c.68A>G	p.Tyr23Cys	missense_variant	2/12	2	NM_018194.6	ENSP00000261458.3		Q5VTY9-1

Frequencies

GnomAD3 genomes

AF:

0.00172

AC:

261

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00584

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

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:

0.00

GnomAD3 exomes

AF:

0.000362

AC:

AN:

251282

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00486

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000142

AC:

207

AN:

1461808

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00472

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000126

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152220

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00583

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000256

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00635

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000461

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 28, 2022	- -

HHAT-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Uncertain

0.73

.;D;.;D;D

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.89

D;D;D;.;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.015

T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.7

M;M;M;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.3

D;D;D;D;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

.;D;.;D;D

Vest4

0.54

MVP

0.73

ClinPred

0.11

GERP RS

2.4

Varity_R

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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