NM_018194.6:c.1007+15375T>A

Variant names:

• chr1-210480030-T-A
• rs2050187
• NM_018194.6:c.1007+15375T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018194.6(HHAT):​c.1007+15375T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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+15375T>A		intron	N/A	NP_060664.2
	HHAT	NM_001170587.3		c.1010+15375T>A		intron	N/A	NP_001164058.1
	HHAT	NM_001122834.4		c.1007+15375T>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.1007+15375T>A		intron	N/A	ENSP00000261458.3
	HHAT	ENST00000545781.2	TSL:1	c.-100-33123T>A		intron	N/A	ENSP00000439229.2
	HHAT	ENST00000545154.5	TSL:2	c.1010+15375T>A		intron	N/A	ENSP00000438468.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.50
PhyloP100		0.45

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: rs2050187; hg19: chr1-210653374;