3-108608096-G-A

Variant names:

• chr3-108608096-G-A
• NM_014648.4:c.40G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014648.4(DZIP3):​c.40G>A​(p.Ala14Thr) 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. 16/22 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)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.397
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042657107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014648.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP3	NM_014648.4	MANE Select	c.40G>A	p.Ala14Thr	missense	Exon 3 of 33	NP_055463.1	Q86Y13-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DZIP3	ENST00000361582.8	TSL:1 MANE Select	c.40G>A	p.Ala14Thr	missense	Exon 3 of 33	ENSP00000355028.3	Q86Y13-1
	DZIP3	ENST00000463306.1	TSL:1	c.40G>A	p.Ala14Thr	missense	Exon 3 of 32	ENSP00000419981.1	Q86Y13-1
	DZIP3	ENST00000927107.1		c.40G>A	p.Ala14Thr	missense	Exon 3 of 33	ENSP00000597166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
PhyloP100		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.023
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-108326943;