chr13-21400414-C-T

Variant names:

• chr13-21400414-C-T
• rs377020404
• NM_001330059.2:c.553G>A

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.553G>A​(p.Val185Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,601,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V185L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ZDHHC20 NM_001330059.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• 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:):

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=0.23232055).

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.553G>A	p.Val185Met	missense	Exon 7 of 13	NP_001316988.1	Q5W0Z9-1
	ZDHHC20	NM_153251.4		c.553G>A	p.Val185Met	missense	Exon 7 of 12	NP_694983.2
	ZDHHC20	NM_001286638.2		c.364G>A	p.Val122Met	missense	Exon 6 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.553G>A	p.Val185Met	missense	Exon 7 of 13	ENSP00000383433.3	Q5W0Z9-1
	ZDHHC20	ENST00000382466.7	TSL:1	c.553G>A	p.Val185Met	missense	Exon 7 of 12	ENSP00000371905.3	Q5W0Z9-3
	ZDHHC20	ENST00000320220.13	TSL:1	c.553G>A	p.Val185Met	missense	Exon 7 of 13	ENSP00000313583.9	Q5W0Z9-4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151776 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000298 AC: 7 AN: 235210 AF XY: 0.0000236

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000176

Gnomad FIN exome AF: 0.0000939

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 24 AN: 1449742 Hom.: 0 Cov.: 30 AF XY: 0.0000194 AC XY: 14 AN XY: 720152

African (AFR) AF: 0.0000305 AC: 1 AN: 32794

American (AMR) AF: 0.00 AC: 0 AN: 42422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25882

East Asian (EAS) AF: 0.000127 AC: 5 AN: 39502

South Asian (SAS) AF: 0.0000608 AC: 5 AN: 82172

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53122

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

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1108132

Other (OTH) AF: 0.0000334 AC: 2 AN: 59968

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151896 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74230

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.00 AC: 0 AN: 15250

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000249 AC: 3

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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	Pathogenic	0.61
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.89	P
Vest4		0.42
MutPred		0.54		Loss of catalytic residue at V122 (P = 0.4438)
MVP		0.29
MPC		1.5
ClinPred		0.33	T
GERP RS		5.9
Varity_R		0.43
gMVP		0.68
Mutation Taster		=67/33	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs377020404; hg19: chr13-21974553;