NM_014648.4:c.776G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014648.4(DZIP3):​c.776G>T​(p.Arg259Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R259Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17577794).

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>T	p.Arg259Leu	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>T	p.Arg259Leu	missense	Exon 9 of 33	ENSP00000355028.3	Q86Y13-1
	DZIP3	ENST00000463306.1	TSL:1	c.776G>T	p.Arg259Leu	missense	Exon 9 of 32	ENSP00000419981.1	Q86Y13-1
	DZIP3	ENST00000927107.1		c.776G>T	p.Arg259Leu	missense	Exon 9 of 33	ENSP00000597166.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1337674 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 661358

African (AFR) AF: 0.00 AC: 0 AN: 29482

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 60158

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5388

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1047522

Other (OTH) AF: 0.00 AC: 0 AN: 54554

GnomAD4 genome Cov.: 31

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		4.2
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.11
Sift	Benign	0.084	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.017	B
Vest4		0.77
MutPred		0.30		Loss of solvent accessibility (P = 0.089)
MVP		0.53
MPC		0.11
ClinPred		0.66	D
GERP RS		4.4
Varity_R		0.14
gMVP		0.54
Mutation Taster		=89/11	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;