rs7527939

Variant names:

• chr1-210362681-C-T
• rs7527939
• NM_018194.6:c.92-171C>T

Variant summary

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

The NM_018194.6(HHAT):​c.92-171C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,076 control chromosomes in the GnomAD database, including 9,200 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 0.29 (9200 hom., cov: 32)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 21 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)

ENSG00000287354 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6	c.92-171C>T		intron_variant	Intron 2 of 11	ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.92-171C>T		intron_variant	Intron 2 of 11	2	NM_018194.6	ENSP00000261458.3

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44813 AN: 151958 Hom.: 9196 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.295 AC: 44852 AN: 152076 Hom.: 9200 Cov.: 32 AF XY: 0.293 AC XY: 21781 AN XY: 74338

African (AFR) AF: 0.588 AC: 24375 AN: 41458

American (AMR) AF: 0.220 AC: 3364 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3470

East Asian (EAS) AF: 0.114 AC: 591 AN: 5174

South Asian (SAS) AF: 0.164 AC: 792 AN: 4816

European-Finnish (FIN) AF: 0.243 AC: 2565 AN: 10572

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11682 AN: 67992

Other (OTH) AF: 0.249 AC: 524 AN: 2108

Alfa AF: 0.215 Hom.: 14976

Bravo AF: 0.307

Asia WGS AF: 0.166 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		2.6
PromoterAI		-0.073	Neutral
Mutation Taster		=99/1	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: rs7527939; hg19: chr1-210536025; COSMIC: COSV54801731; COSMIC: COSV54801731;