rs193920775

Variant names:

• chr22-20141427-C-A
• rs193920775
• NM_013373.4:c.1022C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-20141427-C-A
• chr22-20141427-C-T

Variant summary

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

The NM_013373.4(ZDHHC8):​c.1022C>A​(p.Ala341Asp) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZDHHC8 NM_013373.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.20
• Publications: 0 publications found

Genes affected

ZDHHC8 (HGNC:18474): (zinc finger DHHC-type palmitoyltransferase 8) This gene encodes a four transmembrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein may function as a palmitoyltransferase. Defects in this gene may be associated with a susceptibility to schizophrenia. Alternate splicing of this gene results in multiple transcript variants. A pseudogene of this gene is found on chromosome 22.[provided by RefSeq, May 2010]

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=0.08079192).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013373.4. 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
	ZDHHC8	NM_013373.4	MANE Select	c.1022C>A	p.Ala341Asp	missense	Exon 9 of 11	NP_037505.1	Q9ULC8-1
	ZDHHC8	NM_001185024.2		c.1022C>A	p.Ala341Asp	missense	Exon 9 of 11	NP_001171953.1	Q9ULC8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC8	ENST00000334554.12	TSL:1 MANE Select	c.1022C>A	p.Ala341Asp	missense	Exon 9 of 11	ENSP00000334490.7	Q9ULC8-1
	ZDHHC8	ENST00000405930.3	TSL:2	c.1022C>A	p.Ala341Asp	missense	Exon 9 of 11	ENSP00000384716.3	Q9ULC8-3
	ZDHHC8	ENST00000924012.1		c.1034C>A	p.Ala345Asp	missense	Exon 8 of 10	ENSP00000594071.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.85e-7 AC: 1 AN: 1460736 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 726662

⚠️ 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: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52682

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60360

⚠️ 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

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.054
Eigen_PC	Benign	0.054
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.2
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.047
Sift	Benign	0.044	D
Sift4G	Benign	0.60	T
Polyphen		0.090	B
Vest4		0.28
MutPred		0.20		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.068
MPC		0.54
ClinPred		0.62	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.21
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs193920775; hg19: chr22-20128950; COSMIC: COSV57713473; COSMIC: COSV57713473;