rs3806502

Positions:

• chr2-135530703-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001286569.1(ZRANB3):​c.-1670G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,194 control chromosomes in the GnomAD database, including 11,174 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 0.31 (11174 hom., cov: 32)
  • Exomes 𝑓: 0.094 (0 hom.)
• Consequence: ZRANB3 NM_001286569.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.-8+424G>A		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286569.1	c.-1670G>A		5_prime_UTR_premature_start_codon_gain_variant	1/22		NP_001273498.1
ZRANB3	NM_001286569.1	c.-1670G>A		5_prime_UTR_variant	1/22		NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.-8+424G>A		intron_variant		1	NM_032143.4	ENSP00000264159.6

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46752 AN: 152044 Hom.: 11129 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.286

GnomAD4 exome AF: 0.0938 AC: 3 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.0769 AC XY: 2 AN XY: 26

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

GnomAD4 genome AF: 0.308 AC: 46855 AN: 152162 Hom.: 11174 Cov.: 32 AF XY: 0.310 AC XY: 23079 AN XY: 74394

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.287

Alfa AF: 0.170 Hom.: 6521

Bravo AF: 0.333

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.75

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: rs3806502; hg19: chr2-136288273;