rs1028383

Variant names:

• chr1-210483945-A-T
• rs1028383
• NM_018194.6:c.1007+19290A>T

Variant summary

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

The ENST00000261458.8(HHAT):​c.1007+19290A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,132 control chromosomes in the GnomAD database, including 4,112 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 0.23 (4112 hom., cov: 32)
• Consequence: HHAT ENST00000261458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261458.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	NM_018194.6	MANE Select	c.1007+19290A>T		intron	N/A	NP_060664.2
	HHAT	NM_001170587.3		c.1010+19290A>T		intron	N/A	NP_001164058.1
	HHAT	NM_001122834.4		c.1007+19290A>T		intron	N/A	NP_001116306.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	ENST00000261458.8	TSL:2 MANE Select	c.1007+19290A>T		intron	N/A	ENSP00000261458.3
	HHAT	ENST00000545781.2	TSL:1	c.-100-29208A>T		intron	N/A	ENSP00000439229.2
	HHAT	ENST00000545154.5	TSL:2	c.1010+19290A>T		intron	N/A	ENSP00000438468.1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34776 AN: 152014 Hom.: 4103 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.229 AC: 34803 AN: 152132 Hom.: 4112 Cov.: 32 AF XY: 0.223 AC XY: 16570 AN XY: 74372

African (AFR) AF: 0.224 AC: 9292 AN: 41494

American (AMR) AF: 0.208 AC: 3181 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1035 AN: 3468

East Asian (EAS) AF: 0.105 AC: 544 AN: 5178

South Asian (SAS) AF: 0.128 AC: 620 AN: 4828

European-Finnish (FIN) AF: 0.211 AC: 2236 AN: 10590

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17163 AN: 67986

Other (OTH) AF: 0.251 AC: 529 AN: 2108

Alfa AF: 0.234 Hom.: 593

Bravo AF: 0.232

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.82
PhyloP100		0.027
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: rs1028383; hg19: chr1-210657289;