chr1-210329091-G-C

Variant names:

• chr1-210329091-G-C
• rs1202874500
• NM_018194.6:c.-57G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_001170587.3(HHAT):​c.81G>C​(p.Pro27Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,256,622 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 (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: HHAT NM_001170587.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.01
• 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)

ENSG00000310145 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-210329091-G-C is Benign according to our data. Variant chr1-210329091-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3042732.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=3.01 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170587.3. 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.-57G>C		5_prime_UTR	Exon 1 of 12	NP_060664.2	Q5VTY9-1
	HHAT	NM_001170587.3		c.81G>C	p.Pro27Pro	synonymous	Exon 1 of 11	NP_001164058.1	Q5VTY9-7
	HHAT	NM_001170588.3		c.-57G>C		5_prime_UTR	Exon 1 of 11	NP_001164059.1	Q5VTY9-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HHAT	ENST00000261458.8	TSL:2 MANE Select	c.-57G>C		5_prime_UTR	Exon 1 of 12	ENSP00000261458.3	Q5VTY9-1
	HHAT	ENST00000545154.5	TSL:2	c.81G>C	p.Pro27Pro	synonymous	Exon 1 of 11	ENSP00000438468.1	Q5VTY9-7
	HHAT	ENST00000537898.5	TSL:2	c.-57G>C		5_prime_UTR	Exon 1 of 11	ENSP00000442625.1	Q5VTY9-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000157 AC: 1 AN: 63736 AF XY: 0.0000277

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000269

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 21 AN: 1256622 Hom.: 0 Cov.: 31 AF XY: 0.0000195 AC XY: 12 AN XY: 615124

African (AFR) AF: 0.0000773 AC: 2 AN: 25874

American (AMR) AF: 0.00 AC: 0 AN: 20562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21458

East Asian (EAS) AF: 0.00 AC: 0 AN: 27620

South Asian (SAS) AF: 0.0000165 AC: 1 AN: 60512

European-Finnish (FIN) AF: 0.0000316 AC: 1 AN: 31654

Middle Eastern (MID) AF: 0.000766 AC: 4 AN: 5222

European-Non Finnish (NFE) AF: 0.00000988 AC: 10 AN: 1012126

Other (OTH) AF: 0.0000581 AC: 3 AN: 51594

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HHAT-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		3.0
PromoterAI		0.023	Neutral
Mutation Taster		=280/20	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: rs1202874500; hg19: chr1-210502435;