Genetic Variant NM_024786.3:c.1163C>T (chr5-814779-G-A) – 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_024786.3(ZDHHC11):c.1163C>T(p.Pro388Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,556,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P388S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZDHHC11
NM_024786.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.41

Publications

1 publications found

Variant links:

Genes affected

ZDHHC11 (HGNC:19158): (zinc finger DHHC-type containing 11) Enables signaling adaptor activity. Involved in antiviral innate immune response and positive regulation of defense response to virus by host. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC11 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=0.07230273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024786.3. 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
	ZDHHC11	NM_024786.3	MANE Select	c.1163C>T	p.Pro388Leu	missense	Exon 11 of 13	NP_079062.1	Q9H8X9-1
	ZDHHC11	NM_001393492.1		c.1328C>T	p.Pro443Leu	missense	Exon 11 of 13	NP_001380421.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZDHHC11	ENST00000283441.13	TSL:1 MANE Select	c.1163C>T	p.Pro388Leu	missense	Exon 11 of 13	ENSP00000283441.8	Q9H8X9-1
ZDHHC11	ENST00000503758.6	TSL:5	n.2865C>T		non_coding_transcript_exon	Exon 10 of 12
ZDHHC11	ENST00000507800.1	TSL:5	n.*785C>T		non_coding_transcript_exon	Exon 10 of 12	ENSP00000423817.1	H0Y9D0

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151284

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000140

AC:

AN:

214206

AF XY:

0.0000172

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000391

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000998

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1405328

Hom.:

Cov.:

AF XY:

0.0000115

AC XY:

AN XY:

696800

show subpopulations

African (AFR)

AF:

0.000126

AC:

AN:

31674

American (AMR)

AF:

0.0000279

AC:

AN:

35836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24916

East Asian (EAS)

AF:

0.00

AC:

AN:

37210

South Asian (SAS)

AF:

0.0000391

AC:

AN:

76714

European-Finnish (FIN)

AF:

0.0000191

AC:

AN:

52248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00000831

AC:

AN:

1082992

Other (OTH)

AF:

0.0000689

AC:

AN:

58086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

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:

0.0000198

AC:

AN:

151402

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73990

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.00

AC:

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10458

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67636

Other (OTH)

AF:

0.00

AC:

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

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:

0.0000583

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000165

AC:

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

Benign

0.090

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.020

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0056

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00065

LIST_S2

Benign

0.49

M_CAP

Benign

0.0050

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-5.4

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

REVEL

Benign

0.034

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.19

Vest4

0.090

MVP

0.21

MPC

0.26

ClinPred

0.19

GERP RS

-2.1

Varity_R

0.045

gMVP

0.052

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over