rs1036905545

Variant names:

• chr16-67394713-C-G
• rs1036905545
• NM_001323627.2:c.1346G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-67394713-C-G
• chr16-67394713-C-T

Variant summary

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

The NM_001323627.2(ZDHHC1):​c.1346G>C​(p.Arg449Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,339,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R449Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000060 (0 hom.)
• Consequence: ZDHHC1 NM_001323627.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.663
• Publications: 0 publications found

Genes affected

ZDHHC1 (HGNC:17916): (zinc finger DHHC-type containing 1) Enables palmitoyltransferase activity. Involved in antiviral innate immune response; positive regulation of defense response to virus by host; and protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000299506 (HGNC:):

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 (MetaRNN=0.0551624).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323627.2. 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
	ZDHHC1	NM_001323627.2	MANE Select	c.1346G>C	p.Arg449Pro	missense	Exon 12 of 12	NP_001310556.1	I3L202
	ZDHHC1	NM_013304.3		c.1411G>C	p.Asp471His	missense	Exon 11 of 11	NP_037436.1	Q8WTX9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC1	ENST00000565726.3	TSL:5 MANE Select	c.1346G>C	p.Arg449Pro	missense	Exon 12 of 12	ENSP00000459264.2	I3L202
	ZDHHC1	ENST00000348579.6	TSL:1	c.1411G>C	p.Asp471His	missense	Exon 11 of 11	ENSP00000340299.2	Q8WTX9
	ZDHHC1	ENST00000902881.1		c.1346G>C	p.Arg449Pro	missense	Exon 12 of 12	ENSP00000572940.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151374 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000597 AC: 71 AN: 1188372 Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 39 AN XY: 579248

African (AFR) AF: 0.00 AC: 0 AN: 23572

American (AMR) AF: 0.00 AC: 0 AN: 10704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16882

East Asian (EAS) AF: 0.00 AC: 0 AN: 26982

South Asian (SAS) AF: 0.00 AC: 0 AN: 47732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3284

European-Non Finnish (NFE) AF: 0.0000722 AC: 71 AN: 983494

Other (OTH) AF: 0.00 AC: 0 AN: 47944

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151374 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73958

African (AFR) AF: 0.00 AC: 0 AN: 41080

American (AMR) AF: 0.00 AC: 0 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67894

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.8
DANN	Benign	0.85
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.66
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.15	N
REVEL	Benign	0.075
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.034	D
Polyphen		0.0010	B
Vest4		0.053
MutPred		0.10		Loss of solvent accessibility (P = 0.0217)
MVP		0.030
MPC		1.6
ClinPred		0.55	D
GERP RS		-0.42
Varity_R		0.063
gMVP		0.15
Mutation Taster		=100/0	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: rs1036905545; hg19: chr16-67428616;