rs201523296

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-196198369-G-A
• chr3-196198369-G-C

Variant summary

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

The NM_001039617.2(ZDHHC19):​c.856C>T​(p.Pro286Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000791 in 1,530,610 control chromosomes in the GnomAD database, including 1 homozygotes. 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000083 (1 hom.)
• Consequence: ZDHHC19 NM_001039617.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: 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=0.067104936).

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>T	p.Pro286Ser	missense	Exon 7 of 8	NP_001034706.1	Q8WVZ1-1
	ZDHHC19	NR_135617.2		n.1118C>T		non_coding_transcript_exon	Exon 8 of 9
	ZDHHC19	NR_135618.2		n.997+83C>T		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>T	p.Pro286Ser	missense	Exon 7 of 8	ENSP00000296326.3	Q8WVZ1-1
	ZDHHC19	ENST00000465519.5	TSL:1	n.1446C>T		non_coding_transcript_exon	Exon 7 of 8
	ZDHHC19	ENST00000397544.6	TSL:1	n.*63+83C>T		intron	N/A	ENSP00000380678.2	Q8WVZ1-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000323 AC: 6 AN: 185646 AF XY: 0.0000101

Gnomad AFR exome AF: 0.0000680

Gnomad AMR exome AF: 0.0000425

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000573

Gnomad NFE exome AF: 0.0000339

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000834 AC: 115 AN: 1378416 Hom.: 1 Cov.: 33 AF XY: 0.0000843 AC XY: 57 AN XY: 676398

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

American (AMR) AF: 0.0000309 AC: 1 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: 0.0000199 AC: 1 AN: 50274

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

European-Non Finnish (NFE) AF: 0.000105 AC: 112 AN: 1070716

Other (OTH) AF: 0.0000176 AC: 1 AN: 56692

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152194 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.000131 AC: 2 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.000169 Hom.: 0

Bravo AF: 0.0000453

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000167 AC: 2

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	0.071
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.8
DANN	Benign	0.60
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.011
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.011
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.049	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.24		Loss of glycosylation at P283 (P = 0.0144)
MVP		0.19
MPC		0.29
ClinPred		0.026	T
GERP RS		2.0
Varity_R		0.034
gMVP		0.35
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;