rs12116836

Variant names:

• chr1-210658476-A-G
• rs12116836
• NM_018194.6:c.1391-15812A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018194.6(HHAT):​c.1391-15812A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,114 control chromosomes in the GnomAD database, including 5,998 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 0.26 (5998 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942
• Publications: 5 publications found

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, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6	c.1391-15812A>G		intron_variant	Intron 11 of 11	ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.1391-15812A>G		intron_variant	Intron 11 of 11	2	NM_018194.6	ENSP00000261458.3

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38985 AN: 151996 Hom.: 6001 Cov.: 32

Gnomad AFR AF: 0.0984

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.256 AC: 38990 AN: 152114 Hom.: 5998 Cov.: 32 AF XY: 0.257 AC XY: 19084 AN XY: 74356

African (AFR) AF: 0.0983 AC: 4079 AN: 41516

American (AMR) AF: 0.267 AC: 4086 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1280 AN: 3468

East Asian (EAS) AF: 0.117 AC: 606 AN: 5184

South Asian (SAS) AF: 0.361 AC: 1739 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2942 AN: 10572

Middle Eastern (MID) AF: 0.295 AC: 86 AN: 292

European-Non Finnish (NFE) AF: 0.341 AC: 23185 AN: 67962

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.309 Hom.: 10748

Bravo AF: 0.244

Asia WGS AF: 0.229 AC: 793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.063
DANN	Benign	0.85
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12116836; hg19: chr1-210831820;