rs1465330

Positions:

• chr14-77135476-T-A
• chr14-77135476-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174976.2(ZDHHC22):​c.527-1528A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 145,176 control chromosomes in the GnomAD database, including 14,010 homozygotes. 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: 𝑓 0.44 (14010 hom., cov: 30)
• Consequence: ZDHHC22 NM_174976.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

Genes affected

ZDHHC22 (HGNC:20106): (zinc finger DHHC-type palmitoyltransferase 22) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Located in Golgi apparatus; endoplasmic reticulum; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259164 (HGNC:):

TMEM63C (HGNC:23787): (transmembrane protein 63C) Enables calcium activated cation channel activity. Involved in cation transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Biomarker of focal segmental glomerulosclerosis. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZDHHC22	NM_174976.2	c.527-1528A>T		intron_variant		ENST00000319374.4	NP_777636.2
ZDHHC22	NM_001364172.1	c.527-1528A>T		intron_variant			NP_001351101.1
ZDHHC22	XM_011536661.3	c.527-1528A>T		intron_variant			XP_011534963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZDHHC22	ENST00000319374.4	c.527-1528A>T		intron_variant		1	NM_174976.2	ENSP00000318222.4
ENSG00000259164	ENST00000557752.1	n.136+29632T>A		intron_variant		5		ENSP00000456507.1
TMEM63C	ENST00000557408.5	c.-237+18634T>A		intron_variant		4		ENSP00000450879.1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 64332 AN: 145106 Hom.: 14007 Cov.: 30

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.448

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.443 AC: 64353 AN: 145176 Hom.: 14010 Cov.: 30 AF XY: 0.443 AC XY: 31438 AN XY: 70932

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.445

Alfa AF: 0.466 Hom.: 1763

Bravo AF: 0.421

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.50
DANN	Benign	0.70

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: rs1465330; hg19: chr14-77601819;