Genetic Variant NM_015457.3:c.1040C>G (chr11-57696791-C-G) – 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_015457.3(ZDHHC5):c.1040C>G(p.Pro347Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P347L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZDHHC5
NM_015457.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.07

Publications

1 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:

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_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.1040C>G	p.Pro347Arg	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.1040C>G	p.Pro347Arg	missense	Exon 10 of 12	ENSP00000287169.3	Q9C0B5-1
ZDHHC5	ENST00000527985.6	TSL:1	c.881C>G	p.Pro294Arg	missense	Exon 9 of 11	ENSP00000432202.1
ZDHHC5	ENST00000529480.1	TSL:1	n.1287C>G		non_coding_transcript_exon	Exon 8 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251404

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000205

AC:

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111842

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

0.63

MutationAssessor

Uncertain

2.4

PhyloP100

7.1

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.84

MutPred

0.31

Gain of solvent accessibility (P = 0.0016)

MVP

0.65

MPC

0.74

ClinPred

0.93

GERP RS

4.5

Varity_R

0.25

gMVP

0.55

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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