Genetic Variant NM_001320466.2:c.*3474A>G (chr3-113962104-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001320466.2(ZDHHC23):c.*3474A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,446 control chromosomes in the GnomAD database, including 4,900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4889 hom., cov: 32)

Exomes 𝑓: 0.26 ( 11 hom. )

Consequence

ZDHHC23
NM_001320466.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.554

Publications

15 publications found

Variant links:

Genes affected

ZDHHC23 (HGNC:28654): (zinc finger DHHC-type palmitoyltransferase 23) Predicted to enable protein-cysteine S-palmitoyltransferase activity. Involved in protein localization to plasma membrane and protein palmitoylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ZDHHC23 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320466.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZDHHC23	NM_001320466.2	MANE Select	c.*3474A>G	3_prime_UTR	Exon 5 of 5	NP_001307395.1
ZDHHC23	NR_135271.2		n.2644A>G	non_coding_transcript_exon	Exon 7 of 7
ZDHHC23	NM_001320467.2		c.*3474A>G	3_prime_UTR	Exon 5 of 5	NP_001307396.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZDHHC23	ENST00000638807.2	TSL:5 MANE Select	c.*3474A>G	3_prime_UTR	Exon 5 of 5	ENSP00000492287.2
ZDHHC23	ENST00000330212.7	TSL:1	c.*1371A>G	3_prime_UTR	Exon 6 of 6	ENSP00000330485.3
ZDHHC23	ENST00000478793.1	TSL:2	n.*1110A>G	non_coding_transcript_exon	Exon 7 of 7	ENSP00000420251.1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35073

AN:

151938

Hom.:

4893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0702

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.271

GnomAD4 exome

AF:

0.262

AC:

102

AN:

390

Hom.:

Cov.:

AF XY:

0.261

AC XY:

AN XY:

230

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.267

AC:

101

AN:

378

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.231

AC:

35069

AN:

152056

Hom.:

4889

Cov.:

AF XY:

0.233

AC XY:

17318

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0702

AC:

2912

AN:

41502

American (AMR)

AF:

0.301

AC:

4593

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1253

AN:

3466

East Asian (EAS)

AF:

0.241

AC:

1240

AN:

5146

South Asian (SAS)

AF:

0.335

AC:

1614

AN:

4822

European-Finnish (FIN)

AF:

0.258

AC:

2725

AN:

10554

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.292

AC:

19856

AN:

67976

Other (OTH)

AF:

0.270

AC:

571

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1301

2603

3904

5206

6507

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.262

Hom.:

10207

Bravo

AF:

0.224

Asia WGS

AF:

0.279

AC:

972

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.3

(source)

DANN

Benign

0.76

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over