chr16-67394713-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001323627.2(ZDHHC1):​c.1346G>A​(p.Arg449Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000463 in 1,339,746 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 (★). Synonymous variant affecting the same amino acid position (i.e. R449R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ZDHHC1
NM_001323627.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.663
Variant links:
Genes affected
ZDHHC1 (HGNC:17916): (zinc finger DHHC-type containing 1) Enables palmitoyltransferase activity. Involved in antiviral innate immune response; positive regulation of defense response to virus by host; and protein palmitoylation. Located in Golgi apparatus and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.049999923).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZDHHC1NM_001323627.2 linkc.1346G>A p.Arg449Gln missense_variant Exon 12 of 12 ENST00000565726.3 NP_001310556.1 Q8WTX9I3L202

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZDHHC1ENST00000565726.3 linkc.1346G>A p.Arg449Gln missense_variant Exon 12 of 12 5 NM_001323627.2 ENSP00000459264.2 I3L202
ZDHHC1ENST00000348579.6 linkc.1411G>A p.Asp471Asn missense_variant Exon 11 of 11 1 ENSP00000340299.2 Q8WTX9
ZDHHC1ENST00000566075.1 linkn.901G>A non_coding_transcript_exon_variant Exon 5 of 5 3

Frequencies

GnomAD3 genomes
AF:
0.0000595
AC:
9
AN:
151374
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000133
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000446
AC:
53
AN:
1188372
Hom.:
0
Cov.:
31
AF XY:
0.0000483
AC XY:
28
AN XY:
579248
show subpopulations
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:
0.0000529
Gnomad4 OTH exome
AF:
0.0000209
GnomAD4 genome
AF:
0.0000595
AC:
9
AN:
151374
Hom.:
0
Cov.:
33
AF XY:
0.0000946
AC XY:
7
AN XY:
73958
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000133
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000648
Hom.:
0
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 01, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1411G>A (p.D471N) alteration is located in exon 11 (coding exon 10) of the ZDHHC1 gene. This alteration results from a G to A substitution at nucleotide position 1411, causing the aspartic acid (D) at amino acid position 471 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
0.14
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
6.1
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0082
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.030
N
LIST_S2
Benign
0.38
T
M_CAP
Benign
0.038
D
MetaRNN
Benign
0.050
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.17
N
REVEL
Benign
0.062
Sift
Uncertain
0.018
D
Sift4G
Benign
0.075
T
Polyphen
0.0010
B
Vest4
0.049
MutPred
0.11
Gain of catalytic residue at D471 (P = 0.033);
MVP
0.030
MPC
1.4
ClinPred
0.35
T
GERP RS
-0.42
Varity_R
0.034
gMVP
0.063

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1036905545; hg19: chr16-67428616; API