Variant chr3-108634920-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014648.4(DZIP3):c.866A>T(p.Lys289Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,338 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DZIP3
NM_014648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP3	NM_014648.4 linkuse as main transcript	c.866A>T	p.Lys289Ile	missense_variant	10/33	ENST00000361582.8	NP_055463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DZIP3	ENST00000361582.8 linkuse as main transcript	c.866A>T	p.Lys289Ile	missense_variant	10/33	1	NM_014648.4	ENSP00000355028.3	Q86Y13-1
DZIP3	ENST00000463306.1 linkuse as main transcript	c.866A>T	p.Lys289Ile	missense_variant	10/32	1		ENSP00000419981.1	Q86Y13-1
DZIP3	ENST00000479138.5 linkuse as main transcript	c.866A>T	p.Lys289Ile	missense_variant	10/16	2		ENSP00000418115.1	C9J9M8
DZIP3	ENST00000495008.5 linkuse as main transcript	n.866A>T		non_coding_transcript_exon_variant	10/31	2		ENSP00000418871.1	Q86Y13-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458338

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000508

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 26, 2024

The c.866A>T (p.K289I) alteration is located in exon 10 (coding exon 9) of the DZIP3 gene. This alteration results from a A to T substitution at nucleotide position 866, causing the lysine (K) at amino acid position 289 to be replaced by an isoleucine (I). 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

Pathogenic

0.77

BayesDel_addAF

Benign

0.0077

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.80

.;T;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.81

L;.;L

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.33

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.61

MutPred

0.46

Loss of MoRF binding (P = 0.0218);Loss of MoRF binding (P = 0.0218);Loss of MoRF binding (P = 0.0218);

MVP

0.66

MPC

0.62

ClinPred

0.89

GERP RS

3.9

Varity_R

0.099

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over