3-108629109-G-C

Position:

• chr3-108629109-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014648.4(DZIP3):​c.629G>C​(p.Gly210Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DZIP3 NM_014648.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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=0.114454985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DZIP3	NM_014648.4	c.629G>C	p.Gly210Ala	missense_variant	8/33	ENST00000361582.8	NP_055463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DZIP3	ENST00000361582.8	c.629G>C	p.Gly210Ala	missense_variant	8/33	1	NM_014648.4	ENSP00000355028.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1451228 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 721668

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: 9.02e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.629G>C (p.G210A) alteration is located in exon 8 (coding exon 7) of the DZIP3 gene. This alteration results from a G to C substitution at nucleotide position 629, causing the glycine (G) at amino acid position 210 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T;.;T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.077	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N;.;.;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.38	N;D;N;N
REVEL	Benign	0.024
Sift	Benign	0.083	T;T;T;T
Sift4G	Benign	0.26	T;D;D;T
Polyphen		0.0090	B;.;.;B
Vest4		0.49
MutPred		0.17		Gain of helix (P = 0.062);.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);
MVP		0.37
MPC		0.12
ClinPred		0.14	T
GERP RS		3.4
Varity_R		0.049
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-108347956;