NM_001330059.2:c.628G>C

Variant names:

• chr13-21391821-C-G
• rs561900037
• NM_001330059.2:c.628G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330059.2(ZDHHC20):​c.628G>C​(p.Val210Leu) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V210I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDHHC20 NM_001330059.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

ZDHHC20 (HGNC:20749): (zinc finger DHHC-type palmitoyltransferase 20) Enables protein-cysteine S-palmitoyltransferase activity and zinc ion binding activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in intracellular membrane-bounded organelle and plasma membrane. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000291046 (HGNC:):

MIPEPP3 (HGNC:39458): (mitochondrial intermediate peptidase pseudogene 3)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24278045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330059.2. 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
	ZDHHC20	NM_001330059.2	MANE Select	c.628G>C	p.Val210Leu	missense	Exon 8 of 13	NP_001316988.1	Q5W0Z9-1
	ZDHHC20	NM_153251.4		c.628G>C	p.Val210Leu	missense	Exon 8 of 12	NP_694983.2
	ZDHHC20	NM_001286638.2		c.439G>C	p.Val147Leu	missense	Exon 7 of 11	NP_001273567.1	B4DRN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC20	ENST00000400590.8	TSL:5 MANE Select	c.628G>C	p.Val210Leu	missense	Exon 8 of 13	ENSP00000383433.3	Q5W0Z9-1
	ZDHHC20	ENST00000382466.7	TSL:1	c.628G>C	p.Val210Leu	missense	Exon 8 of 12	ENSP00000371905.3	Q5W0Z9-3
	ZDHHC20	ENST00000320220.13	TSL:1	c.628G>C	p.Val210Leu	missense	Exon 8 of 13	ENSP00000313583.9	Q5W0Z9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.17	T
Sift4G	Benign	0.17	T
Polyphen		0.040	B
Vest4		0.53
MutPred		0.30		Loss of ubiquitination at K144 (P = 0.0777)
MVP		0.099
MPC		0.83
ClinPred		0.56	D
GERP RS		3.5
Varity_R		0.39
gMVP		0.76
Mutation Taster		=43/57	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs561900037; hg19: chr13-21965960;