rs972219371

Variant names:

• chr3-108608112-G-A
• rs972219371
• NM_014648.4:c.56G>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.56G>A​(p.Arg19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,808 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0910
• 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=0.03856191).

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.56G>A	p.Arg19Lys	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.56G>A	p.Arg19Lys	missense	Exon 3 of 33	ENSP00000355028.3	Q86Y13-1
	DZIP3	ENST00000463306.1	TSL:1	c.56G>A	p.Arg19Lys	missense	Exon 3 of 32	ENSP00000419981.1	Q86Y13-1
	DZIP3	ENST00000927107.1		c.56G>A	p.Arg19Lys	missense	Exon 3 of 33	ENSP00000597166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460808 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39602

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111428

Other (OTH) AF: 0.00 AC: 0 AN: 60330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.066
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.44
DEOGEN2	Benign	0.023	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.091
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.024
Sift	Benign	0.17	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.13		Gain of ubiquitination at R19 (P = 0.0025)
MVP		0.15
MPC		0.089
ClinPred		0.065	T
GERP RS		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.13
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs972219371; hg19: chr3-108326959;