rs1413822794
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM4BP6_ModerateBS2
The NM_016032.4(ZDHHC9):c.1064_1065insCCCACAGCC(p.Pro355_Pro356insProGlnPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,097,902 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000025 ( 0 hom. 10 hem. )
Failed GnomAD Quality Control
Consequence
ZDHHC9
NM_016032.4 disruptive_inframe_insertion
NM_016032.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.07
Publications
0 publications found
Genes affected
ZDHHC9 (HGNC:18475): (zinc finger DHHC-type palmitoyltransferase 9) This gene encodes an integral membrane protein that is a member of the zinc finger DHHC domain-containing protein family. The encoded protein forms a complex with golgin subfamily A member 7 and functions as a palmitoyltransferase. This protein specifically palmitoylates HRAS and NRAS. Mutations in this gene are associated with X-linked cognitive disability. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, May 2010]
ZDHHC9 Gene-Disease associations (from GenCC):
- syndromic X-linked intellectual disability Raymond typeInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen
- X-linked intellectual disability with marfanoid habitusInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_016032.4.
BP6
Variant X-129806400-T-TGGCTGTGGG is Benign according to our data. Variant chrX-129806400-T-TGGCTGTGGG is described in ClinVar as Likely_benign. ClinVar VariationId is 470198.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 10 XL gene
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016032.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ZDHHC9 | NM_016032.4 | MANE Select | c.1064_1065insCCCACAGCC | p.Pro355_Pro356insProGlnPro | disruptive_inframe_insertion | Exon 11 of 11 | NP_057116.2 | ||
| ZDHHC9 | NM_001008222.3 | c.1064_1065insCCCACAGCC | p.Pro355_Pro356insProGlnPro | disruptive_inframe_insertion | Exon 10 of 10 | NP_001008223.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ZDHHC9 | ENST00000357166.11 | TSL:1 MANE Select | c.1064_1065insCCCACAGCC | p.Pro355_Pro356insProGlnPro | disruptive_inframe_insertion | Exon 11 of 11 | ENSP00000349689.6 | ||
| ZDHHC9 | ENST00000371064.7 | TSL:1 | c.1064_1065insCCCACAGCC | p.Pro355_Pro356insProGlnPro | disruptive_inframe_insertion | Exon 10 of 10 | ENSP00000360103.3 |
Frequencies
GnomAD3 genomes 0.00000893 AC: 1AN: 111957Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
111957
Hom.:
Cov.:
22
Gnomad AFR
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GnomAD2 exomes AF: 0.0000163 AC: 3AN: 183505 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
183505
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.0000246 AC: 27AN: 1097902Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 10AN XY: 363260 show subpopulations
GnomAD4 exome
AF:
AC:
27
AN:
1097902
Hom.:
Cov.:
30
AF XY:
AC XY:
10
AN XY:
363260
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26399
American (AMR)
AF:
AC:
24
AN:
35204
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19385
East Asian (EAS)
AF:
AC:
0
AN:
30206
South Asian (SAS)
AF:
AC:
0
AN:
54137
European-Finnish (FIN)
AF:
AC:
0
AN:
40532
Middle Eastern (MID)
AF:
AC:
0
AN:
4131
European-Non Finnish (NFE)
AF:
AC:
0
AN:
841819
Other (OTH)
AF:
AC:
3
AN:
46089
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.419
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome 0.00000893 AC: 1AN: 111957Hom.: 0 Cov.: 22 AF XY: 0.0000293 AC XY: 1AN XY: 34109 show subpopulations
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
111957
Hom.:
Cov.:
22
AF XY:
AC XY:
1
AN XY:
34109
show subpopulations
African (AFR)
AF:
AC:
0
AN:
30737
American (AMR)
AF:
AC:
1
AN:
10551
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2644
East Asian (EAS)
AF:
AC:
0
AN:
3581
South Asian (SAS)
AF:
AC:
0
AN:
2676
European-Finnish (FIN)
AF:
AC:
0
AN:
6115
Middle Eastern (MID)
AF:
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
AC:
0
AN:
53219
Other (OTH)
AF:
AC:
0
AN:
1511
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Syndromic X-linked intellectual disability Raymond type (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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