NM_014648.4:c.812A>G

Variant names:

• chr3-108633068-A-G
• rs139745617
• NM_014648.4:c.812A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014648.4(DZIP3):​c.812A>G​(p.Tyr271Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00021 in 1,455,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.95
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021271408).

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.812A>G	p.Tyr271Cys	missense	Exon 9 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.812A>G	p.Tyr271Cys	missense	Exon 9 of 33	ENSP00000355028.3	Q86Y13-1
	DZIP3	ENST00000463306.1	TSL:1	c.812A>G	p.Tyr271Cys	missense	Exon 9 of 32	ENSP00000419981.1	Q86Y13-1
	DZIP3	ENST00000927107.1		c.812A>G	p.Tyr271Cys	missense	Exon 9 of 33	ENSP00000597166.1

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151690 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000281 AC: 53 AN: 188518 AF XY: 0.000213

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00402

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.000250

GnomAD4 exome AF: 0.000209 AC: 273 AN: 1303942 Hom.: 0 Cov.: 27 AF XY: 0.000231 AC XY: 149 AN XY: 643806

African (AFR) AF: 0.00 AC: 0 AN: 28086

American (AMR) AF: 0.00 AC: 0 AN: 28884

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 89 AN: 22022

East Asian (EAS) AF: 0.00 AC: 0 AN: 33394

South Asian (SAS) AF: 0.000167 AC: 9 AN: 53748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48040

Middle Eastern (MID) AF: 0.000383 AC: 2 AN: 5222

European-Non Finnish (NFE) AF: 0.000153 AC: 158 AN: 1031706

Other (OTH) AF: 0.000284 AC: 15 AN: 52840

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151802 Hom.: 0 Cov.: 31 AF XY: 0.000162 AC XY: 12 AN XY: 74214

African (AFR) AF: 0.0000482 AC: 2 AN: 41510

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10370

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67902

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000373 Hom.: 1

Bravo AF: 0.000215

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.000280 AC: 34

Asia WGS AF: 0.000290 AC: 1 AN: 3458

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	0.34
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.31
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.81	L
PhyloP100		3.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MVP		0.78
MPC		0.44
ClinPred		0.16	T
GERP RS		4.2
Varity_R		0.39
gMVP		0.60
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs139745617; hg19: chr3-108351915;