chr1-210478223-T-C

Variant names:

• chr1-210478223-T-C
• rs761174
• NM_018194.6:c.1007+13568T>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.1007+13568T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,144 control chromosomes in the GnomAD database, including 48,151 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 0.79 (48151 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 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.1007+13568T>C		intron	N/A	NP_060664.2
	HHAT	NM_001170587.3		c.1010+13568T>C		intron	N/A	NP_001164058.1
	HHAT	NM_001122834.4		c.1007+13568T>C		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+13568T>C		intron	N/A	ENSP00000261458.3
	HHAT	ENST00000545781.2	TSL:1	c.-100-34930T>C		intron	N/A	ENSP00000439229.2
	HHAT	ENST00000545154.5	TSL:2	c.1010+13568T>C		intron	N/A	ENSP00000438468.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120346 AN: 152026 Hom.: 48107 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.744

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.792 AC: 120452 AN: 152144 Hom.: 48151 Cov.: 32 AF XY: 0.793 AC XY: 58946 AN XY: 74358

African (AFR) AF: 0.888 AC: 36847 AN: 41498

American (AMR) AF: 0.815 AC: 12460 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2669 AN: 3468

East Asian (EAS) AF: 0.993 AC: 5146 AN: 5180

South Asian (SAS) AF: 0.745 AC: 3589 AN: 4816

European-Finnish (FIN) AF: 0.743 AC: 7871 AN: 10588

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49395 AN: 67996

Other (OTH) AF: 0.789 AC: 1667 AN: 2112

Alfa AF: 0.768 Hom.: 67956

Bravo AF: 0.807

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.036
DANN	Benign	0.35
PhyloP100		-0.63
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: rs761174; hg19: chr1-210651567;