22-20140031-A-C

Variant names:

• chr22-20140031-A-C
• rs175174
• NM_013373.4:c.558-84A>C

Variant summary

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

The NM_013373.4(ZDHHC8):​c.558-84A>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZDHHC8 NM_013373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 44 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.558-84A>C		intron	N/A	NP_037505.1	Q9ULC8-1
	ZDHHC8	NM_001185024.2		c.558-84A>C		intron	N/A	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.558-84A>C		intron	N/A	ENSP00000334490.7	Q9ULC8-1
	ZDHHC8	ENST00000405930.3	TSL:2	c.558-84A>C		intron	N/A	ENSP00000384716.3	Q9ULC8-3
	ZDHHC8	ENST00000924012.1		c.672+24A>C		intron	N/A	ENSP00000594071.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.96e-7 AC: 1 AN: 1436324 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 715494

African (AFR) AF: 0.00 AC: 0 AN: 33026

American (AMR) AF: 0.00 AC: 0 AN: 44102

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39440

South Asian (SAS) AF: 0.00 AC: 0 AN: 85540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.14e-7 AC: 1 AN: 1093964

Other (OTH) AF: 0.00 AC: 0 AN: 59548

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	16
DANN	Benign	0.52
PhyloP100		-0.033
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.28		Position offset: 14

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

Other links and lift over

dbSNP: rs175174; hg19: chr22-20127554;