chr13-21421159-T-C

Position:

• chr13-21421159-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001330059.2(ZDHHC20):​c.151A>G​(p.Thr51Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZDHHC20 NM_001330059.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.66

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0489541).
• BP6: Variant 13-21421159-T-C is Benign according to our data. Variant chr13-21421159-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534765.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZDHHC20	NM_001330059.2	c.151A>G	p.Thr51Ala	missense_variant	3/13	ENST00000400590.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZDHHC20	ENST00000400590.8	c.151A>G	p.Thr51Ala	missense_variant	3/13	5	NM_001330059.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Benign	0.44
DEOGEN2	Benign	0.0032	.;T;.;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.36	T;.;T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.049	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.11	N;N;N;N
MutationTaster	Benign	1.0	D;N;N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.17	N;N;N;N
REVEL	Benign	0.054
Sift	Benign	0.57	T;T;T;T
Sift4G	Benign	0.58	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.16
MutPred		0.41		Loss of glycosylation at T51 (P = 0.0215);Loss of glycosylation at T51 (P = 0.0215);Loss of glycosylation at T51 (P = 0.0215);Loss of glycosylation at T51 (P = 0.0215);
MVP		0.040
MPC		0.55
ClinPred		0.080	T
GERP RS		3.7
Varity_R		0.054
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-21995298;