chr3-196198369-G-C

Variant names:

• chr3-196198369-G-C
• rs201523296
• NM_001039617.2:c.856C>G

Variant summary

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

The NM_001039617.2(ZDHHC19):​c.856C>G​(p.Pro286Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000725 in 1,378,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. P286S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: ZDHHC19 NM_001039617.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 0 publications found

Genes affected

ZDHHC19 (HGNC:20713): (zinc finger DHHC-type palmitoyltransferase 19) Enables protein-cysteine S-palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi membrane; endoplasmic reticulum; and perinucleolar compartment. [provided by Alliance of Genome Resources, Apr 2022]

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=0.076125056).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039617.2. 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
	ZDHHC19	NM_001039617.2	MANE Select	c.856C>G	p.Pro286Ala	missense	Exon 7 of 8	NP_001034706.1	Q8WVZ1-1
	ZDHHC19	NR_135617.2		n.1118C>G		non_coding_transcript_exon	Exon 8 of 9
	ZDHHC19	NR_135618.2		n.997+83C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC19	ENST00000296326.8	TSL:5 MANE Select	c.856C>G	p.Pro286Ala	missense	Exon 7 of 8	ENSP00000296326.3	Q8WVZ1-1
	ZDHHC19	ENST00000465519.5	TSL:1	n.1446C>G		non_coding_transcript_exon	Exon 7 of 8
	ZDHHC19	ENST00000397544.6	TSL:1	n.*63+83C>G		intron	N/A	ENSP00000380678.2	Q8WVZ1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.25e-7 AC: 1 AN: 1378416 Hom.: 0 Cov.: 33 AF XY: 0.00000148 AC XY: 1 AN XY: 676398

African (AFR) AF: 0.00 AC: 0 AN: 30854

American (AMR) AF: 0.00 AC: 0 AN: 32316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20468

East Asian (EAS) AF: 0.00 AC: 0 AN: 38860

South Asian (SAS) AF: 0.00 AC: 0 AN: 72912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5324

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1070716

Other (OTH) AF: 0.00 AC: 0 AN: 56692

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.3
DANN	Benign	0.55
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.011
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.010
Sift	Uncertain	0.019	D
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.23		Loss of glycosylation at P283 (P = 0.0144)
MVP		0.18
MPC		0.28
ClinPred		0.042	T
GERP RS		2.0
Varity_R		0.034
gMVP		0.23
Mutation Taster		=97/3	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: rs201523296; hg19: chr3-195925240;