Genetic Variant ZDHHC11:p.Val373Leu (chr5-819554-C-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.1117G>T(p.Val373Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,286 control chromosomes in the GnomAD database, including 1 homozygotes. 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. V373I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 1 hom. )

Consequence

ZDHHC11
NM_024786.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

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=0.06942454).

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.1117G>T	p.Val373Leu	missense	Exon 10 of 13	NP_079062.1	Q9H8X9-1
	ZDHHC11	NM_001393492.1		c.1282G>T	p.Val428Leu	missense	Exon 10 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.1117G>T	p.Val373Leu	missense	Exon 10 of 13	ENSP00000283441.8	Q9H8X9-1
ZDHHC11	ENST00000503758.6	TSL:5	n.2819G>T		non_coding_transcript_exon	Exon 9 of 12
ZDHHC11	ENST00000507800.1	TSL:5	n.*739G>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000423817.1	H0Y9D0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251116

AF XY:

0.00000737

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458286

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.00

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000451

AC:

AN:

1109004

Other (OTH)

AF:

0.00

AC:

AN:

60258

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

Exome Hom

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

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.012

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.36

M_CAP

Benign

0.0015

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-1.2

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.13

REVEL

Benign

0.0080

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.053

Vest4

0.080

MutPred

0.21

Loss of sheet (P = 0.0315)

MVP

0.072

MPC

0.072

ClinPred

0.057

GERP RS

-0.84

Varity_R

0.10

gMVP

0.029

Mutation Taster

=100/0

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

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