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: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC22	NM_174976.2	c.527-1528A>G		intron_variant	Intron 2 of 2	ENST00000319374.4	NP_777636.2
ZDHHC22	NM_001364172.1	c.527-1528A>G		intron_variant	Intron 2 of 2		NP_001351101.1
ZDHHC22	XM_011536661.3	c.527-1528A>G		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>G		intron_variant	Intron 2 of 2	1	NM_174976.2	ENSP00000318222.4
ENSG00000259164	ENST00000557752.1	n.136+29632T>C		intron_variant	Intron 2 of 5	5		ENSP00000456507.1
TMEM63C	ENST00000557408.5	c.-237+18634T>C		intron_variant	Intron 1 of 3	4		ENSP00000450879.1

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 v4.3

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;