Genetic Variant DZIP3:p.Asp264Asn (chr3-108633046-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014648.4(DZIP3):c.790G>A(p.Asp264Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000176 in 1,477,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

DZIP3
NM_014648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

DZIP3 (HGNC:30938): (DAZ interacting zinc finger protein 3) Enables several functions, including phosphatase binding activity; polyubiquitin modification-dependent protein binding activity; and ubiquitin-protein transferase activity. Involved in protein polyubiquitination. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DZIP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.14118537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP3	NM_014648.4 link	c.790G>A	p.Asp264Asn	missense_variant	Exon 9 of 33	ENST00000361582.8	NP_055463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DZIP3	ENST00000361582.8 link	c.790G>A	p.Asp264Asn	missense_variant	Exon 9 of 33	1	NM_014648.4	ENSP00000355028.3	Q86Y13-1
DZIP3	ENST00000463306.1 link	c.790G>A	p.Asp264Asn	missense_variant	Exon 9 of 32	1		ENSP00000419981.1	Q86Y13-1
DZIP3	ENST00000479138.5 link	c.790G>A	p.Asp264Asn	missense_variant	Exon 9 of 16	2		ENSP00000418115.1	C9J9M8
DZIP3	ENST00000495008.5 link	n.790G>A		non_coding_transcript_exon_variant	Exon 9 of 31	2		ENSP00000418871.1	Q86Y13-2

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151572

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:

0.0000884

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000963

AC:

AN:

197336

Hom.:

AF XY:

0.0000741

AC XY:

AN XY:

107992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000478

Gnomad NFE exome

AF:

0.000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000192

AC:

254

AN:

1326290

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

112

AN XY:

655196

show subpopulations

Gnomad4 AFR exome

AF:

0.0000690

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:

0.0000204

Gnomad4 NFE exome

AF:

0.000233

Gnomad4 OTH exome

AF:

0.000148

GnomAD4 genome

AF:

0.0000396

AC:

AN:

151572

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74000

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:

0.0000884

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.790G>A (p.D264N) alteration is located in exon 9 (coding exon 8) of the DZIP3 gene. This alteration results from a G to A substitution at nucleotide position 790, causing the aspartic acid (D) at amino acid position 264 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T;T

Eigen

Benign

-0.094

Eigen_PC

Benign

0.083

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

L;.;L

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.023

Sift

Benign

0.066

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.041

B;.;B

Vest4

0.68

MVP

0.54

MPC

0.088

ClinPred

0.13

GERP RS

4.4

Varity_R

0.12

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over