3-196207475-G-C

Variant names:

• chr3-196207475-G-C
• NM_001039617.2:c.610C>G

Variant summary

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

The NM_001039617.2(ZDHHC19):​c.610C>G​(p.Leu204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,416,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: ZDHHC19 NM_001039617.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.271

Genes affected

ZDHHC19 (HGNC:20713): (zinc finger DHHC-type palmitoyltransferase 19) Enables protein-cysteine S-palmitoyltransferase activity. Involved in peptidyl-L-cysteine S-palmitoylation. Located in Golgi membrane; endoplasmic reticulum; and perinucleolar compartment. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14965269).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZDHHC19	NM_001039617.2	c.610C>G	p.Leu204Val	missense_variant	Exon 5 of 8	ENST00000296326.8	NP_001034706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZDHHC19	ENST00000296326.8	c.610C>G	p.Leu204Val	missense_variant	Exon 5 of 8	5	NM_001039617.2	ENSP00000296326.3
ZDHHC19	ENST00000397544.6	n.610C>G		non_coding_transcript_exon_variant	Exon 5 of 8	1		ENSP00000380678.2
ZDHHC19	ENST00000465519.5	n.1205C>G		non_coding_transcript_exon_variant	Exon 5 of 8	1
ZDHHC19	ENST00000438232.5	n.610C>G		non_coding_transcript_exon_variant	Exon 5 of 9	2		ENSP00000393710.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000282 AC: 4 AN: 1416890 Hom.: 0 Cov.: 30 AF XY: 0.00000285 AC XY: 2 AN XY: 700860

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610C>G (p.L204V) alteration is located in exon 5 (coding exon 5) of the ZDHHC19 gene. This alteration results from a C to G substitution at nucleotide position 610, causing the leucine (L) at amino acid position 204 to be replaced by a valine (V). 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	0.063
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.64	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.066
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.090	T
Polyphen		0.0010	B
Vest4		0.21
MutPred		0.43		Loss of glycosylation at S200 (P = 0.0865);
MVP		0.085
MPC		0.32
ClinPred		0.39	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.12
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr3-195934346;