Variant 3-108634887-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014648.4(DZIP3):c.833T>C(p.Met278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DZIP3
NM_014648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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=0.16197187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP3	NM_014648.4 linkuse as main transcript	c.833T>C	p.Met278Thr	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.833T>C	p.Met278Thr	missense_variant	10/33	1	NM_014648.4	ENSP00000355028.3	Q86Y13-1
DZIP3	ENST00000463306.1 linkuse as main transcript	c.833T>C	p.Met278Thr	missense_variant	10/32	1		ENSP00000419981.1	Q86Y13-1
DZIP3	ENST00000479138.5 linkuse as main transcript	c.833T>C	p.Met278Thr	missense_variant	10/16	2		ENSP00000418115.1	C9J9M8
DZIP3	ENST00000495008.5 linkuse as main transcript	n.833T>C		non_coding_transcript_exon_variant	10/31	2		ENSP00000418871.1	Q86Y13-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246720

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454336

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723478

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

May 10, 2024

The c.833T>C (p.M278T) alteration is located in exon 10 (coding exon 9) of the DZIP3 gene. This alteration results from a T to C substitution at nucleotide position 833, causing the methionine (M) at amino acid position 278 to be replaced by a threonine (T). 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

Benign

0.21

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.033

T;T;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

0.010

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.74

T;D;T

Polyphen

0.0060

B;P;B

Vest4

0.55

MutPred

0.32

Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);

MVP

0.39

MPC

0.12

ClinPred

0.24

GERP RS

3.9

Varity_R

0.10

gMVP

0.42

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