NM_018194.6:c.1391-10788C>T

Variant names:

• chr1-210663500-C-T
• rs1890843
• NM_018194.6:c.1391-10788C>T

Variant summary

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

The NM_018194.6(HHAT):​c.1391-10788C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,202 control chromosomes in the GnomAD database, including 60,464 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 0.89 (60464 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.140
• Publications: 7 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6	c.1391-10788C>T		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.1391-10788C>T		intron_variant	Intron 11 of 11	2	NM_018194.6	ENSP00000261458.3

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135418 AN: 152084 Hom.: 60416 Cov.: 32

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.938

Gnomad ASJ AF: 0.924

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.916

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.890 AC: 135524 AN: 152202 Hom.: 60464 Cov.: 32 AF XY: 0.889 AC XY: 66188 AN XY: 74426

African (AFR) AF: 0.849 AC: 35226 AN: 41506

American (AMR) AF: 0.938 AC: 14344 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3206 AN: 3470

East Asian (EAS) AF: 0.825 AC: 4266 AN: 5170

South Asian (SAS) AF: 0.871 AC: 4203 AN: 4824

European-Finnish (FIN) AF: 0.851 AC: 9021 AN: 10596

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.916 AC: 62308 AN: 68024

Other (OTH) AF: 0.915 AC: 1936 AN: 2116

Alfa AF: 0.910 Hom.: 287511

Bravo AF: 0.897

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.2
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs1890843; hg19: chr1-210836847;