chr3-108633020-T-G

Position:

• chr3-108633020-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014648.4(DZIP3):​c.764T>G​(p.Leu255Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29710352).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP3	NM_014648.4	c.764T>G	p.Leu255Arg	missense_variant	9/33	ENST00000361582.8	NP_055463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP3	ENST00000361582.8	c.764T>G	p.Leu255Arg	missense_variant	9/33	1	NM_014648.4	ENSP00000355028.3
DZIP3	ENST00000463306.1	c.764T>G	p.Leu255Arg	missense_variant	9/32	1		ENSP00000419981.1
DZIP3	ENST00000479138.5	c.764T>G	p.Leu255Arg	missense_variant	9/16	2		ENSP00000418115.1
DZIP3	ENST00000495008.5	n.764T>G		non_coding_transcript_exon_variant	9/31	2		ENSP00000418871.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.764T>G (p.L255R) alteration is located in exon 9 (coding exon 8) of the DZIP3 gene. This alteration results from a T to G substitution at nucleotide position 764, causing the leucine (L) at amino acid position 255 to be replaced by an arginine (R). 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	0.43
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T;T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N;.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.55	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.039	D;T;D
Sift4G	Uncertain	0.048	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.85
MutPred		0.41		Gain of catalytic residue at L255 (P = 0.0117);Gain of catalytic residue at L255 (P = 0.0117);Gain of catalytic residue at L255 (P = 0.0117);
MVP		0.68
MPC		0.44
ClinPred		0.78	D
GERP RS		3.5
Varity_R		0.14
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-108351867;