rs10746432

chr1-210664344-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018194.6(HHAT):c.1391-9944G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,082 control chromosomes in the GnomAD database, including 12,810 homozygotes. 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: 𝑓 0.41 (12810 hom., cov: 33)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HHAT	NM_018194.6	c.1391-9944G>A		intron_variant		ENST00000261458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HHAT	ENST00000261458.8	c.1391-9944G>A		intron_variant		2	NM_018194.6	P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61654 AN: 151964 Hom.: 12805 Cov.: 33

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.407

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.406 AC: 61712 AN: 152082 Hom.: 12810 Cov.: 33 AF XY: 0.404 AC XY: 30049 AN XY: 74320

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.384

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.411

Alfa AF: 0.433 Hom.: 28916

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10746432; hg19: chr1-210837691;