Genetic Variant NM_014648.4:c.456+10A>G (chr3-108624534-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014648.4(DZIP3):c.456+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,476,258 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 9 hom. )

Consequence

DZIP3
NM_014648.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.61

Publications

0 publications found

Variant links:

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]

DZIP3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-108624534-A-G is Benign according to our data. Variant chr3-108624534-A-G is described in ClinVar as Benign. ClinVar VariationId is 719661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00686 (1044/152278) while in subpopulation AFR AF = 0.0237 (984/41570). AF 95% confidence interval is 0.0224. There are 5 homozygotes in GnomAd4. There are 484 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

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.456+10A>G		intron	N/A	NP_055463.1	Q86Y13-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DZIP3	ENST00000361582.8	TSL:1 MANE Select	c.456+10A>G	intron	N/A	ENSP00000355028.3	Q86Y13-1
DZIP3	ENST00000463306.1	TSL:1	c.456+10A>G	intron	N/A	ENSP00000419981.1	Q86Y13-1
DZIP3	ENST00000927107.1		c.456+10A>G	intron	N/A	ENSP00000597166.1

Frequencies

GnomAD3 genomes

AF:

0.00682

AC:

1038

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00323

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00526

GnomAD2 exomes

AF:

0.00162

AC:

355

AN:

218928

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000923

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000484

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.000717

AC:

949

AN:

1323980

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

401

AN XY:

663904

show subpopulations

African (AFR)

AF:

0.0267

AC:

787

AN:

29472

American (AMR)

AF:

0.00121

AC:

AN:

38074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24732

East Asian (EAS)

AF:

0.00

AC:

AN:

36922

South Asian (SAS)

AF:

0.000131

AC:

AN:

76596

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52676

Middle Eastern (MID)

AF:

0.000730

AC:

AN:

5478

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

1004622

Other (OTH)

AF:

0.00157

AC:

AN:

55408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

130

173

216

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00686

AC:

1044

AN:

152278

Hom.:

Cov.:

AF XY:

0.00650

AC XY:

484

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0237

AC:

984

AN:

41570

American (AMR)

AF:

0.00268

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000621

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00345

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67998

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00395

Hom.:

Bravo

AF:

0.00748

Asia WGS

AF:

0.000876

AC:

AN:

3440

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

5.3

(source)

DANN

Benign

0.87

PhyloP100

1.6

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over