Genetic Variant ZDHHC19:p.Thr98Lys (chr3-196209491-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001039617.2(ZDHHC19):c.293C>A(p.Thr98Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,614 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. T98M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZDHHC19
NM_001039617.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.417

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:

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ACMG classification

Classification was made for transcript

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=0.071064234).

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.293C>A	p.Thr98Lys	missense	Exon 3 of 8	NP_001034706.1	Q8WVZ1-1
ZDHHC19	NR_135617.2		n.378C>A		non_coding_transcript_exon	Exon 3 of 9
ZDHHC19	NR_135618.2		n.378C>A		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.293C>A	p.Thr98Lys	missense	Exon 3 of 8	ENSP00000296326.3	Q8WVZ1-1
ZDHHC19	ENST00000397544.6	TSL:1	n.293C>A		non_coding_transcript_exon	Exon 3 of 8	ENSP00000380678.2	Q8WVZ1-3
ZDHHC19	ENST00000465519.5	TSL:1	n.286C>A		non_coding_transcript_exon	Exon 3 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000409

AC:

AN:

244496

AF XY:

0.00000750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460614

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26092

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52920

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111708

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.67

CADD

Benign

2.2

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.51

M_CAP

Benign

0.0055

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

-0.42

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

REVEL

Benign

0.081

Sift

Benign

0.10

Sift4G

Benign

0.17

Polyphen

0.50

Vest4

0.14

MutPred

0.52

Gain of methylation at T98 (P = 0.0078)

MVP

0.014

MPC

0.46

ClinPred

0.076

GERP RS

-5.6

Varity_R

0.067

gMVP

0.32

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over