13-21391842-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330059.2(ZDHHC20):c.607G>A(p.Asp203Asn) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZDHHC20 NM_001330059.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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]

MIPEPP3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15229192).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC20	NM_001330059.2	c.607G>A	p.Asp203Asn	missense_variant	8/13	ENST00000400590.8
MIPEPP3	NR_046461.1	n.638+25C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC20	ENST00000400590.8	c.607G>A	p.Asp203Asn	missense_variant	8/13	5	NM_001330059.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2021

The c.607G>A (p.D203N) alteration is located in exon 8 (coding exon 8) of the ZDHHC20 gene. This alteration results from a G to A substitution at nucleotide position 607, causing the aspartic acid (D) at amino acid position 203 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D;D;.;D;D
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.96	L;.;L;L;L
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.7	N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.25	T;T;T;T;T
Sift4G	Benign	0.33	T;T;T;T;T
Polyphen		0.0020	B;B;.;.;.
Vest4		0.27
MutPred		0.41		.;Gain of methylation at R142 (P = 0.0672);.;.;.;
MVP		0.095
MPC		0.55
ClinPred		0.43	T
GERP RS		4.4
Varity_R		0.20
gMVP		0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs1472706047; hg19: chr13-21965981; COSMIC: COSV57186263; COSMIC: COSV57186263;