5-850416-A-G

Position:

• chr5-850416-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024786.3(ZDHHC11):​c.187T>C​(p.Phe63Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZDHHC11 NM_024786.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.198

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]

BRD9 (HGNC:25818): (bromodomain containing 9) Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03786862).
• BP6: Variant 5-850416-A-G is Benign according to our data. Variant chr5-850416-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3334218.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC11	NM_024786.3	c.187T>C	p.Phe63Leu	missense_variant	1/13	ENST00000283441.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC11	ENST00000283441.13	c.187T>C	p.Phe63Leu	missense_variant	1/13	1	NM_024786.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251192 Hom.: 0 AF XY: 0.0000294 AC XY: 4 AN XY: 135864

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461314 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.28
DANN	Benign	0.37
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0015	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.38	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	2.0	N
REVEL	Benign	0.037
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.026
MutPred		0.56		Gain of catalytic residue at F63 (P = 0.0899);
MVP		0.26
MPC		0.034
ClinPred		0.013	T
GERP RS		-3.7
Varity_R		0.047
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs761077971; hg19: chr5-850531;