chr13-21391821-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001330059.2(ZDHHC20):​c.628G>A​(p.Val210Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,612,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: ZDHHC20 NM_001330059.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041686982).

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>A	p.Val210Ile	missense	Exon 8 of 13	NP_001316988.1	Q5W0Z9-1
	ZDHHC20	NM_153251.4		c.628G>A	p.Val210Ile	missense	Exon 8 of 12	NP_694983.2
	ZDHHC20	NM_001286638.2		c.439G>A	p.Val147Ile	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>A	p.Val210Ile	missense	Exon 8 of 13	ENSP00000383433.3	Q5W0Z9-1
	ZDHHC20	ENST00000382466.7	TSL:1	c.628G>A	p.Val210Ile	missense	Exon 8 of 12	ENSP00000371905.3	Q5W0Z9-3
	ZDHHC20	ENST00000320220.13	TSL:1	c.628G>A	p.Val210Ile	missense	Exon 8 of 13	ENSP00000313583.9	Q5W0Z9-4

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152050 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000729 AC: 18 AN: 247058 AF XY: 0.0000672

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000168

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000685 AC: 100 AN: 1460422 Hom.: 0 Cov.: 31 AF XY: 0.0000675 AC XY: 49 AN XY: 726316

African (AFR) AF: 0.0000599 AC: 2 AN: 33402

American (AMR) AF: 0.0000225 AC: 1 AN: 44526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39650

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000612 AC: 68 AN: 1111426

Other (OTH) AF: 0.0000331 AC: 2 AN: 60348

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152168 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74366

African (AFR) AF: 0.0000963 AC: 4 AN: 41522

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10558

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000501 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000108 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Benign	0.43
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.18	N
PhyloP100		1.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.053
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.013	B
Vest4		0.19
MutPred		0.28		Loss of ubiquitination at K144 (P = 0.0896)
MVP		0.040
MPC		0.48
ClinPred		0.023	T
GERP RS		3.5
Varity_R		0.064
gMVP		0.49
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV100203510; COSMIC: COSV100203510;