16-67394893-C-G

Variant names:

• chr16-67394893-C-G
• rs749577256
• NM_001323627.2:c.1166G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001323627.2(ZDHHC1):​c.1166G>C​(p.Gly389Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000709 in 1,410,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZDHHC1 NM_001323627.2 missense, splice_region
• Scores: Splicing: ADA: 0.6012
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081284136).

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.1166G>C	p.Gly389Ala	missense splice_region	Exon 12 of 12	NP_001310556.1	I3L202
	ZDHHC1	NM_013304.3		c.1231G>C	p.Gly411Arg	missense splice_region	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.1166G>C	p.Gly389Ala	missense splice_region	Exon 12 of 12	ENSP00000459264.2	I3L202
	ZDHHC1	ENST00000348579.6	TSL:1	c.1231G>C	p.Gly411Arg	missense splice_region	Exon 11 of 11	ENSP00000340299.2	Q8WTX9
	ZDHHC1	ENST00000902881.1		c.1166G>C	p.Gly389Ala	missense splice_region	Exon 12 of 12	ENSP00000572940.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.09e-7 AC: 1 AN: 1410528 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 697224

African (AFR) AF: 0.00 AC: 0 AN: 32176

American (AMR) AF: 0.00 AC: 0 AN: 38346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24548

East Asian (EAS) AF: 0.00 AC: 0 AN: 37642

South Asian (SAS) AF: 0.00 AC: 0 AN: 80766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44860

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 9.19e-7 AC: 1 AN: 1088436

Other (OTH) AF: 0.00 AC: 0 AN: 58122

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.5
DANN	Uncertain	0.99
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.081	T
PhyloP100		-0.064
MVP		0.048
ClinPred		0.61	D
GERP RS		-0.92
Varity_R		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.60
dbscSNV1_RF	Benign	0.43
SpliceAI score (max)		0.17		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: rs749577256; hg19: chr16-67428796;