dbSNP rs768575668: ZDHHC5:p.Thr350Asn (chr11-57696800-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015457.3(ZDHHC5):c.1049C>A(p.Thr350Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T350I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZDHHC5
NM_015457.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.07

Publications

0 publications found

Variant links:

Genes affected

ZDHHC5 (HGNC:18472): (zinc finger DHHC-type palmitoyltransferase 5) Enables palmitoyltransferase activity. Involved in positive regulation of pattern recognition receptor signaling pathway and positive regulation of protein localization to plasma membrane. Acts upstream of or within protein palmitoylation. Located in phagocytic vesicle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC5 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ZDHHC5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37267303).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015457.3. 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
	ZDHHC5	NM_015457.3	MANE Select	c.1049C>A	p.Thr350Asn	missense	Exon 10 of 12	NP_056272.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC5	ENST00000287169.8	TSL:1 MANE Select	c.1049C>A	p.Thr350Asn	missense	Exon 10 of 12	ENSP00000287169.3	Q9C0B5-1
ZDHHC5	ENST00000527985.6	TSL:1	c.890C>A	p.Thr297Asn	missense	Exon 9 of 11	ENSP00000432202.1
ZDHHC5	ENST00000529480.1	TSL:1	n.1296C>A		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461738

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727160

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111906

Other (OTH)

AF:

0.00

AC:

AN:

60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

Uncertain

0.44

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Pathogenic

0.68

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.061

MetaRNN

Benign

0.37

MetaSVM

Uncertain

0.21

MutationAssessor

Benign

1.7

PhyloP100

7.1

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.7

REVEL

Benign

0.20

Sift

Uncertain

0.014

Sift4G

Uncertain

0.026

Polyphen

0.95

Vest4

0.60

MutPred

0.12

Loss of glycosylation at T350 (P = 0.0092)

MVP

0.35

MPC

0.59

ClinPred

0.86

GERP RS

5.5

Varity_R

0.17

gMVP

0.44

Mutation Taster

=43/57

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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