ENST00000426968.2:c.-22C>T

Variant names:

• chr1-210387476-C-T
• rs539661329
• ENST00000426968.2:c.-22C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The ENST00000426968.2(HHAT):​c.-22C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: HHAT ENST00000426968.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -7.00
• Publications: 0 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, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000287157 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-210387476-C-T is Benign according to our data. Variant chr1-210387476-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1986330.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000426968.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	NM_018194.6	MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 4 of 12	NP_060664.2	Q5VTY9-1
	HHAT	NM_001170587.3		c.171C>T	p.Thr57Thr	synonymous	Exon 3 of 11	NP_001164058.1	Q5VTY9-7
	HHAT	NM_001122834.4		c.168C>T	p.Thr56Thr	synonymous	Exon 4 of 12	NP_001116306.1	Q5VTY9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	ENST00000426968.2	TSL:1	c.-22C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000413399.1	A0A075B6R5
	HHAT	ENST00000545781.2	TSL:1	c.-206C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000439229.2	F5H2Y1
	HHAT	ENST00000261458.8	TSL:2 MANE Select	c.168C>T	p.Thr56Thr	synonymous	Exon 4 of 12	ENSP00000261458.3	Q5VTY9-1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000278 AC: 7 AN: 251412 AF XY: 0.0000368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000322 AC: 47 AN: 1461694 Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32 AN XY: 727164

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111852

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74434

African (AFR) AF: 0.00 AC: 0 AN: 41528

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.63
PhyloP100		-7.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=300/0	polymorphism

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: rs539661329; hg19: chr1-210560820; COSMIC: COSV99803197;