1-210664344-G-A

Variant names:

• chr1-210664344-G-A
• rs10746432
• NM_018194.6:c.1391-9944G>A

Variant summary

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

The NM_018194.6(HHAT):​c.1391-9944G>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
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018194.6. 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.1391-9944G>A		intron	N/A	NP_060664.2
	HHAT	NM_001170587.3		c.1394-9944G>A		intron	N/A	NP_001164058.1
	HHAT	NM_001122834.4		c.1391-9944G>A		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.1391-9944G>A		intron	N/A	ENSP00000261458.3
	HHAT	ENST00000545154.5	TSL:2	c.1394-9944G>A		intron	N/A	ENSP00000438468.1
	HHAT	ENST00000367010.5	TSL:2	c.1391-9944G>A		intron	N/A	ENSP00000355977.1

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

African (AFR) AF: 0.342 AC: 14177 AN: 41496

American (AMR) AF: 0.431 AC: 6589 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3472

East Asian (EAS) AF: 0.384 AC: 1986 AN: 5174

South Asian (SAS) AF: 0.290 AC: 1392 AN: 4806

European-Finnish (FIN) AF: 0.470 AC: 4959 AN: 10554

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.441 AC: 29970 AN: 67976

Other (OTH) AF: 0.411 AC: 868 AN: 2114

Alfa AF: 0.428 Hom.: 44768

Bravo AF: 0.403

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.17
PhyloP100		-0.085

Splicing

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

Other links and lift over

dbSNP: rs10746432; hg19: chr1-210837691;