chr3-108633032-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DZIP3	NM_014648.4	c.776G>T	p.Arg259Leu	missense_variant	Exon 9 of 33	ENST00000361582.8	NP_055463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DZIP3	ENST00000361582.8	c.776G>T	p.Arg259Leu	missense_variant	Exon 9 of 33	1	NM_014648.4	ENSP00000355028.3
DZIP3	ENST00000463306.1	c.776G>T	p.Arg259Leu	missense_variant	Exon 9 of 32	1		ENSP00000419981.1
DZIP3	ENST00000479138.5	c.776G>T	p.Arg259Leu	missense_variant	Exon 9 of 16	2		ENSP00000418115.1
DZIP3	ENST00000495008.5	n.776G>T		non_coding_transcript_exon_variant	Exon 9 of 31	2		ENSP00000418871.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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 v4.3

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;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.86	.;D;D
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.084	T;T;T
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.017	B;.;B
Vest4		0.77
MutPred		0.30		Loss of solvent accessibility (P = 0.089);Loss of solvent accessibility (P = 0.089);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs201597941; hg19: chr3-108351879;