Genetic Variant DZIP3:p.Ser244Asn (chr3-108632987-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014648.4(DZIP3):c.731G>A(p.Ser244Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000381 in 1,311,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

DZIP3
NM_014648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.518

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054545492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP3	NM_014648.4 link	c.731G>A	p.Ser244Asn	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.731G>A	p.Ser244Asn	missense_variant	Exon 9 of 33	1	NM_014648.4	ENSP00000355028.3	Q86Y13-1
DZIP3	ENST00000463306.1 link	c.731G>A	p.Ser244Asn	missense_variant	Exon 9 of 32	1		ENSP00000419981.1	Q86Y13-1
DZIP3	ENST00000479138.5 link	c.731G>A	p.Ser244Asn	missense_variant	Exon 9 of 16	2		ENSP00000418115.1	C9J9M8
DZIP3	ENST00000495008.5 link	n.731G>A		non_coding_transcript_exon_variant	Exon 9 of 31	2		ENSP00000418871.1	Q86Y13-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000101

AC:

AN:

197772

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

108184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000154

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:

0.00000381

AC:

AN:

1311778

Hom.:

Cov.:

AF XY:

0.00000460

AC XY:

AN XY:

652210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000854

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000196

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 11, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.731G>A (p.S244N) 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 731, causing the serine (S) at amino acid position 244 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

Benign

0.058

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.9

DANN

Benign

0.18

DEOGEN2

Benign

0.026

T;T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.74

T;T;T

Polyphen

0.0060

B;.;B

Vest4

0.12

MutPred

0.20

Gain of ubiquitination at K248 (P = 0.0797);Gain of ubiquitination at K248 (P = 0.0797);Gain of ubiquitination at K248 (P = 0.0797);

MVP

0.54

MPC

0.080

ClinPred

0.041

GERP RS

1.6

Varity_R

0.054

gMVP

0.20

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