dbSNP rs775743190: ZDHHC9:c.881+3G>A (chrX-129811403-C-T) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_016032.4(ZDHHC9):c.881+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,203,657 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000028 ( 0 hom. 6 hem. )

Consequence

ZDHHC9
NM_016032.4 splice_region, intron

Scores

Splicing: ADA: 0.00005593

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.609

Publications

0 publications found

Variant links:

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 type
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
X-linked intellectual disability with marfanoid habitus
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ZDHHC9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant X-129811403-C-T is Benign according to our data. Variant chrX-129811403-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 537741.

BS2

High Hemizygotes in GnomAdExome4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZDHHC9	NM_016032.4	MANE Select	c.881+3G>A		splice_region intron	N/A	NP_057116.2	Q9Y397
	ZDHHC9	NM_001008222.3		c.881+3G>A		splice_region intron	N/A	NP_001008223.1	Q9Y397

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZDHHC9	ENST00000357166.11	TSL:1 MANE Select	c.881+3G>A	splice_region intron	N/A	ENSP00000349689.6	Q9Y397
ZDHHC9	ENST00000371064.7	TSL:1	c.881+3G>A	splice_region intron	N/A	ENSP00000360103.3	Q9Y397
ZDHHC9	ENST00000860167.1		c.971+3G>A	splice_region intron	N/A	ENSP00000530226.1

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110767

Hom.:

Cov.:

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:

0.0000756

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000276

AC:

AN:

181248

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000728

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000493

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1092890

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

358478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26305

American (AMR)

AF:

0.00

AC:

AN:

34975

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19300

East Asian (EAS)

AF:

0.00

AC:

AN:

30170

South Asian (SAS)

AF:

0.00

AC:

AN:

53697

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4125

European-Non Finnish (NFE)

AF:

0.0000370

AC:

AN:

837906

Other (OTH)

AF:

0.00

AC:

AN:

45918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110767

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32975

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30390

American (AMR)

AF:

0.00

AC:

AN:

10384

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2633

East Asian (EAS)

AF:

0.00

AC:

AN:

3543

South Asian (SAS)

AF:

0.00

AC:

AN:

2566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5897

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.0000756

AC:

AN:

52943

Other (OTH)

AF:

0.00

AC:

AN:

1492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autism spectrum disorder (1)

Syndromic X-linked intellectual disability Raymond type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000056

dbscSNV1_RF

Benign

0.030

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over