5-850389-C-T

Variant names:

• chr5-850389-C-T
• NM_024786.3:c.214G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024786.3(ZDHHC11):​c.214G>A​(p.Ala72Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZDHHC11 NM_024786.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.700
• 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]

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065849215).

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.214G>A	p.Ala72Thr	missense	Exon 1 of 13	NP_079062.1	Q9H8X9-1
	ZDHHC11	NM_001393492.1		c.214G>A	p.Ala72Thr	missense	Exon 1 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.214G>A	p.Ala72Thr	missense	Exon 1 of 13	ENSP00000283441.8	Q9H8X9-1
	ZDHHC11	ENST00000685990.1		c.214G>A	p.Ala72Thr	missense	Exon 2 of 4	ENSP00000509570.1	A0A8I5KQG6
	BRD9	ENST00000493082.5	TSL:5	n.652G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.7
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.70
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.050
Sift	Benign	0.32	T
Sift4G	Benign	0.19	T
Polyphen		0.15	B
Vest4		0.026
MutPred		0.49		Loss of stability (P = 0.0623)
MVP		0.24
MPC		0.044
ClinPred		0.25	T
GERP RS		0.90
Varity_R		0.053
gMVP		0.43
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

hg19: chr5-850504;