Genetic Variant ZDHHC19:p.Pro122Ser (chr3-196209420-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001039617.2(ZDHHC19):c.364C>T(p.Pro122Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,608,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZDHHC19
NM_001039617.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.76

Publications

0 publications found

Variant links:

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]

ZDHHC19 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC19	NM_001039617.2	MANE Select	c.364C>T	p.Pro122Ser	missense	Exon 3 of 8	NP_001034706.1	Q8WVZ1-1
ZDHHC19	NR_135617.2		n.449C>T		non_coding_transcript_exon	Exon 3 of 9
ZDHHC19	NR_135618.2		n.449C>T		non_coding_transcript_exon	Exon 3 of 8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC19	ENST00000296326.8	TSL:5 MANE Select	c.364C>T	p.Pro122Ser	missense	Exon 3 of 8	ENSP00000296326.3	Q8WVZ1-1
ZDHHC19	ENST00000397544.6	TSL:1	n.364C>T		non_coding_transcript_exon	Exon 3 of 8	ENSP00000380678.2	Q8WVZ1-3
ZDHHC19	ENST00000465519.5	TSL:1	n.357C>T		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

234988

AF XY:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456370

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.0000229

AC:

AN:

43738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25920

East Asian (EAS)

AF:

0.00

AC:

AN:

39506

South Asian (SAS)

AF:

0.00

AC:

AN:

85054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109980

Other (OTH)

AF:

0.00

AC:

AN:

60160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152254

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5204

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.82

M_CAP

Benign

0.0054

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

PhyloP100

5.8

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.29

Sift

Benign

0.032

Sift4G

Benign

0.16

Polyphen

0.89

Vest4

0.50

MutPred

0.70

Loss of glycosylation at P123 (P = 0.0242)

MVP

0.15

MPC

0.92

ClinPred

1.0

GERP RS

5.8

Varity_R

0.33

gMVP

0.78

Mutation Taster

=76/24

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over