rs737388

Positions:

• chr2-135315641-T-C

Variant summary

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

The NM_032143.4(ZRANB3):​c.678-111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 787,776 control chromosomes in the GnomAD database, including 989 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 0.062 (577 hom., cov: 32)
  • Exomes 𝑓: 0.023 (412 hom.)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.678-111A>G		intron_variant		ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.678-111A>G		intron_variant			NP_001273497.1
ZRANB3	NM_001286569.1	c.-780-111A>G		intron_variant			NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.678-111A>G		intron_variant		1	NM_032143.4	ENSP00000264159.6

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9429 AN: 152172 Hom.: 577 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0406

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0513

GnomAD4 exome AF: 0.0229 AC: 14552 AN: 635486 Hom.: 412 AF XY: 0.0229 AC XY: 7268 AN XY: 317788

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0364

Gnomad4 ASJ exome AF: 0.0685

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.0154

Gnomad4 NFE exome AF: 0.0162

Gnomad4 OTH exome AF: 0.0342

GnomAD4 genome AF: 0.0620 AC: 9446 AN: 152290 Hom.: 577 Cov.: 32 AF XY: 0.0601 AC XY: 4479 AN XY: 74474

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.0562

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.0128

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0517

Alfa AF: 0.0433 Hom.: 75

Bravo AF: 0.0685

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.77

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: rs737388; hg19: chr2-136073211;