GeneBe

2-135350269-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032143.4(ZRANB3):​c.360-54C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000848 in 1,179,612 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

ZRANB3
NM_032143.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.874

Publications

0 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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZRANB3NM_032143.4 linkc.360-54C>A intron_variant Intron 4 of 20 ENST00000264159.11 NP_115519.2
ZRANB3NM_001286568.2 linkc.360-54C>A intron_variant Intron 4 of 20 NP_001273497.1
ZRANB3NM_001286569.1 linkc.-1098-54C>A intron_variant Intron 4 of 21 NP_001273498.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZRANB3ENST00000264159.11 linkc.360-54C>A intron_variant Intron 4 of 20 1 NM_032143.4 ENSP00000264159.6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.48e-7
AC:
1
AN:
1179612
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
586558
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
27174
American (AMR)
AF:
0.00
AC:
0
AN:
32222
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22818
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34512
South Asian (SAS)
AF:
0.00
AC:
0
AN:
70782
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
37834
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4568
European-Non Finnish (NFE)
AF:
0.00000111
AC:
1
AN:
899100
Other (OTH)
AF:
0.00
AC:
0
AN:
50602
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
7.4
DANN
Benign
0.67
PhyloP100
0.87

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

Other links and lift over

dbSNP: rs10496734; hg19: chr2-136107839; API