rs10863838

Variant names:

• chr1-210510839-T-C
• rs10863838
• NM_018194.6:c.1008-2314T>C

Variant summary

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

The NM_018194.6(HHAT):​c.1008-2314T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 152,086 control chromosomes in the GnomAD database, including 14,895 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 0.44 (14895 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6	c.1008-2314T>C		intron_variant	Intron 8 of 11	ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.1008-2314T>C		intron_variant	Intron 8 of 11	2	NM_018194.6	ENSP00000261458.3

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67030 AN: 151968 Hom.: 14889 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.441 AC: 67076 AN: 152086 Hom.: 14895 Cov.: 32 AF XY: 0.440 AC XY: 32732 AN XY: 74356

African (AFR) AF: 0.408 AC: 16943 AN: 41478

American (AMR) AF: 0.437 AC: 6678 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1775 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2967 AN: 5174

South Asian (SAS) AF: 0.344 AC: 1657 AN: 4810

European-Finnish (FIN) AF: 0.476 AC: 5036 AN: 10578

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30604 AN: 67978

Other (OTH) AF: 0.453 AC: 955 AN: 2110

Alfa AF: 0.451 Hom.: 2643

Bravo AF: 0.442

Asia WGS AF: 0.414 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.73
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10863838; hg19: chr1-210684183;