Genetic Variant HHAT:c.159+15C>A (chr1-210362934-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_018194.6(HHAT):c.159+15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,566,260 control chromosomes in the GnomAD database, including 14,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1050 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13921 hom. )

Consequence

HHAT
NM_018194.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.225

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:

ENSG00000287354 (HGNC:):

ENSG00000287354 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 (BayesDel_noAF=-0.89).

BP6

Variant 1-210362934-C-A is Benign according to our data. Variant chr1-210362934-C-A is described in ClinVar as [Benign]. Clinvar id is 1599919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6 link	c.159+15C>A		intron_variant	Intron 3 of 11	ENST00000261458.8	NP_060664.2	Q5VTY9-1B7Z5N1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8 link	c.159+15C>A		intron_variant	Intron 3 of 11	2	NM_018194.6	ENSP00000261458.3		Q5VTY9-1

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16141

AN:

151986

Hom.:

1047

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0994

Gnomad ASJ

AF:

0.0982

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.139

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.112

AC:

28164

AN:

250442

Hom.:

1940

AF XY:

0.117

AC XY:

15847

AN XY:

135312

show subpopulations

Gnomad AFR exome

AF:

0.0361

Gnomad AMR exome

AF:

0.0722

Gnomad ASJ exome

AF:

0.100

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.150

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.135

AC:

190599

AN:

1414156

Hom.:

13921

Cov.:

AF XY:

0.135

AC XY:

95530

AN XY:

706380

show subpopulations

Gnomad4 AFR exome

AF:

0.0354

Gnomad4 AMR exome

AF:

0.0748

Gnomad4 ASJ exome

AF:

0.0979

Gnomad4 EAS exome

AF:

0.000987

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.149

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.106

AC:

16154

AN:

152104

Hom.:

1050

Cov.:

AF XY:

0.106

AC XY:

7880

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0389

Gnomad4 AMR

AF:

0.0993

Gnomad4 ASJ

AF:

0.0982

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.139

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.104

Alfa

AF:

0.121

Hom.:

303

Bravo

AF:

0.0982

Asia WGS

AF:

0.0650

AC:

228

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 03, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.59

DANN

Benign

0.74

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