5-814779-G-T

Variant names:

• chr5-814779-G-T
• rs778647556
• NM_024786.3:c.1163C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024786.3(ZDHHC11):​c.1163C>A​(p.Pro388Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,405,328 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. 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. P388L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZDHHC11 NM_024786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.41
• Publications: 0 publications found

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]

ACMG classification

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=0.14332482).

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>A	p.Pro388Gln	missense	Exon 11 of 13	NP_079062.1	Q9H8X9-1
	ZDHHC11	NM_001393492.1		c.1328C>A	p.Pro443Gln	missense	Exon 11 of 13	NP_001380421.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC11	ENST00000283441.13	TSL:1 MANE Select	c.1163C>A	p.Pro388Gln	missense	Exon 11 of 13	ENSP00000283441.8	Q9H8X9-1
	ZDHHC11	ENST00000503758.6	TSL:5	n.2865C>A		non_coding_transcript_exon	Exon 10 of 12
	ZDHHC11	ENST00000507800.1	TSL:5	n.*785C>A		non_coding_transcript_exon	Exon 10 of 12	ENSP00000423817.1	H0Y9D0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000142 AC: 2 AN: 1405328 Hom.: 0 Cov.: 30 AF XY: 0.00000287 AC XY: 2 AN XY: 696800

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

African (AFR) AF: 0.00 AC: 0 AN: 31674

American (AMR) AF: 0.00 AC: 0 AN: 35836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24916

East Asian (EAS) AF: 0.00 AC: 0 AN: 37210

South Asian (SAS) AF: 0.0000130 AC: 1 AN: 76714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1082992

Other (OTH) AF: 0.00 AC: 0 AN: 58086

⚠️ 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.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.0090
DANN	Benign	0.80
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-5.4
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.14
MutPred		0.19		Gain of helix (P = 0.0349)
MVP		0.25
MPC		0.31
ClinPred		0.38	T
GERP RS		-2.1
Varity_R		0.057
gMVP		0.058
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs778647556; hg19: chr5-814894;