Genetic Variant ZRANB3:c.360-54C>T (chr2-135350269-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032143.4(ZRANB3):c.360-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,330,092 control chromosomes in the GnomAD database, including 15,141 homozygotes. 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: 𝑓 0.19 ( 3676 hom., cov: 32)

Exomes 𝑓: 0.11 ( 11465 hom. )

Consequence

ZRANB3
NM_032143.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.874

Publications

9 publications found

Variant links:

Genes affected

ZRANB3 (HGNC:25249): (zinc finger RANBP2-type containing 3) Enables ATP-dependent DNA/DNA annealing activity; K63-linked polyubiquitin modification-dependent protein binding activity; and endodeoxyribonuclease activity. Involved in several processes, including DNA metabolic process; DNA rewinding; and negative regulation of DNA recombination. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZRANB3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032143.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZRANB3	NM_032143.4	MANE Select	c.360-54C>T	intron	N/A	NP_115519.2
ZRANB3	NM_001286568.2		c.360-54C>T	intron	N/A	NP_001273497.1
ZRANB3	NM_001286569.1		c.-1098-54C>T	intron	N/A	NP_001273498.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.360-54C>T	intron	N/A	ENSP00000264159.6
ZRANB3	ENST00000401392.5	TSL:1	c.360-54C>T	intron	N/A	ENSP00000383979.1
ZRANB3	ENST00000536680.5	TSL:1	c.-1098-54C>T	intron	N/A	ENSP00000441320.2

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28814

AN:

151830

Hom.:

3665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.335

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.247

Gnomad ASJ

AF:

0.188

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.0750

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.0956

Gnomad OTH

AF:

0.195

GnomAD4 exome

AF:

0.112

AC:

132483

AN:

1178144

Hom.:

11465

AF XY:

0.118

AC XY:

69407

AN XY:

585856

show subpopulations

African (AFR)

AF:

0.346

AC:

9377

AN:

27124

American (AMR)

AF:

0.247

AC:

7943

AN:

32156

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

4430

AN:

22782

East Asian (EAS)

AF:

0.216

AC:

7452

AN:

34496

South Asian (SAS)

AF:

0.298

AC:

21033

AN:

70662

European-Finnish (FIN)

AF:

0.0743

AC:

2810

AN:

37802

Middle Eastern (MID)

AF:

0.206

AC:

939

AN:

4560

European-Non Finnish (NFE)

AF:

0.0794

AC:

71336

AN:

898008

Other (OTH)

AF:

0.142

AC:

7163

AN:

50554

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

5155

10310

15464

20619

25774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2618

5236

7854

10472

13090

<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:

0.190

AC:

28862

AN:

151948

Hom.:

3676

Cov.:

AF XY:

0.193

AC XY:

14355

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.335

AC:

13876

AN:

41366

American (AMR)

AF:

0.247

AC:

3766

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.188

AC:

653

AN:

3470

East Asian (EAS)

AF:

0.219

AC:

1131

AN:

5170

South Asian (SAS)

AF:

0.331

AC:

1594

AN:

4812

European-Finnish (FIN)

AF:

0.0750

AC:

794

AN:

10586

Middle Eastern (MID)

AF:

0.209

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0956

AC:

6497

AN:

67980

Other (OTH)

AF:

0.198

AC:

416

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1115

2230

3344

4459

5574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.125

Hom.:

831

Bravo

AF:

0.205

Asia WGS

AF:

0.296

AC:

1027

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

7.8

(source)

DANN

Benign

0.73

PhyloP100

0.87

Mutation Taster

=100/0

polymorphism (auto)

(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

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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