chr1-210344738-C-T

Variant names:

• chr1-210344738-C-T
• rs6696657
• NM_018194.6:c.-43-4195C>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.-43-4195C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,922 control chromosomes in the GnomAD database, including 13,925 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 0.42 (13925 hom., cov: 31)
• Consequence: HHAT NM_018194.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HHAT	NM_018194.6	c.-43-4195C>T		intron_variant	Intron 1 of 11	ENST00000261458.8	NP_060664.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HHAT	ENST00000261458.8	c.-43-4195C>T		intron_variant	Intron 1 of 11	2	NM_018194.6	ENSP00000261458.3

Frequencies

GnomAD3 genomes AF: 0.422 AC: 63998 AN: 151804 Hom.: 13899 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.422 AC: 64080 AN: 151922 Hom.: 13925 Cov.: 31 AF XY: 0.420 AC XY: 31203 AN XY: 74228

African (AFR) AF: 0.478 AC: 19805 AN: 41412

American (AMR) AF: 0.379 AC: 5786 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1269 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1028 AN: 5164

South Asian (SAS) AF: 0.455 AC: 2185 AN: 4802

European-Finnish (FIN) AF: 0.413 AC: 4356 AN: 10546

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28242 AN: 67962

Other (OTH) AF: 0.419 AC: 884 AN: 2110

Alfa AF: 0.418 Hom.: 37985

Bravo AF: 0.420

Asia WGS AF: 0.353 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.080
DANN	Benign	0.48
PhyloP100		-1.7
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: rs6696657; hg19: chr1-210518082; COSMIC: COSV54809065;