rs201597941

Variant names:

• chr3-108633032-G-A
• rs201597941
• NM_014648.4:c.776G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-108633032-G-A
• chr3-108633032-G-T

Variant summary

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

The NM_014648.4(DZIP3):​c.776G>A​(p.Arg259Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000221 in 1,489,482 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.23
• Publications: 1 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=0.035321593).

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.776G>A	p.Arg259Gln	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.776G>A	p.Arg259Gln	missense	Exon 9 of 33	ENSP00000355028.3	Q86Y13-1
	DZIP3	ENST00000463306.1	TSL:1	c.776G>A	p.Arg259Gln	missense	Exon 9 of 32	ENSP00000419981.1	Q86Y13-1
	DZIP3	ENST00000927107.1		c.776G>A	p.Arg259Gln	missense	Exon 9 of 33	ENSP00000597166.1

Frequencies

GnomAD3 genomes AF: 0.0000923 AC: 14 AN: 151698 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 30 AN: 204108 AF XY: 0.000197

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.000220

GnomAD4 exome AF: 0.000237 AC: 317 AN: 1337668 Hom.: 1 Cov.: 27 AF XY: 0.000245 AC XY: 162 AN XY: 661352

African (AFR) AF: 0.0000678 AC: 2 AN: 29482

American (AMR) AF: 0.0000302 AC: 1 AN: 33148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23374

East Asian (EAS) AF: 0.00 AC: 0 AN: 34428

South Asian (SAS) AF: 0.000748 AC: 45 AN: 60154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49620

Middle Eastern (MID) AF: 0.000186 AC: 1 AN: 5388

European-Non Finnish (NFE) AF: 0.000242 AC: 254 AN: 1047520

Other (OTH) AF: 0.000257 AC: 14 AN: 54554

GnomAD4 genome AF: 0.0000790 AC: 12 AN: 151814 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74220

African (AFR) AF: 0.0000241 AC: 1 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.0000907

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000117 AC: 1

ExAC AF: 0.000206 AC: 25

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	Uncertain	0.36
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.036	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.2
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.11
Sift	Benign	0.082	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.59
MVP		0.65
MPC		0.27
ClinPred		0.22	T
GERP RS		4.4
Varity_R		0.098
gMVP		0.39
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: rs201597941; hg19: chr3-108351879; COSMIC: COSV64311687; COSMIC: COSV64311687;