14-77135476-T-C

Variant names:

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

Variant summary

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

The NM_174976.2(ZDHHC22):​c.527-1528A>G 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: 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: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P

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 (BayesDel_noAF=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174976.2. 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
	ZDHHC22	NM_174976.2	MANE Select	c.527-1528A>G		intron	N/A	NP_777636.2	Q8N966
	ZDHHC22	NM_001364172.1		c.527-1528A>G		intron	N/A	NP_001351101.1	Q8N966

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC22	ENST00000319374.4	TSL:1 MANE Select	c.527-1528A>G		intron	N/A	ENSP00000318222.4	Q8N966
	ENSG00000259164	ENST00000557752.1	TSL:5	n.136+29632T>C		intron	N/A	ENSP00000456507.1	H3BS24
	ZDHHC22	ENST00000924336.1		c.527-1528A>G		intron	N/A	ENSP00000594395.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 1763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		0.29

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;