14-77135476-T-A

Variant names:

• chr14-77135476-T-A
• rs1465330
• NM_174976.2:c.527-1528A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TMEM63C Gene-Disease associations (from GenCC):

• spastic paraplegia 87, autosomal recessive

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZDHHC22	NM_174976.2	c.527-1528A>T		intron_variant	Intron 2 of 2	ENST00000319374.4	NP_777636.2
ZDHHC22	NM_001364172.1	c.527-1528A>T		intron_variant	Intron 2 of 2		NP_001351101.1
ZDHHC22	XM_011536661.3	c.527-1528A>T		intron_variant	Intron 2 of 2		XP_011534963.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC22	ENST00000319374.4	c.527-1528A>T		intron_variant	Intron 2 of 2	1	NM_174976.2	ENSP00000318222.4
ENSG00000259164	ENST00000557752.1	n.136+29632T>A		intron_variant	Intron 2 of 5	5		ENSP00000456507.1
TMEM63C	ENST00000557408.5	c.-237+18634T>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.349 AC: 12916 AN: 36974

American (AMR) AF: 0.446 AC: 6664 AN: 14956

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1727 AN: 3418

East Asian (EAS) AF: 0.459 AC: 2184 AN: 4762

South Asian (SAS) AF: 0.397 AC: 1838 AN: 4632

European-Finnish (FIN) AF: 0.483 AC: 4848 AN: 10028

Middle Eastern (MID) AF: 0.433 AC: 122 AN: 282

European-Non Finnish (NFE) AF: 0.489 AC: 32900 AN: 67232

Other (OTH) AF: 0.445 AC: 883 AN: 1984

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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs1465330; hg19: chr14-77601819;