rs10496734

chr2-135350269-G-Achr2-135350269-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.874

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZRANB3	NM_032143.4	c.360-54C>T		intron_variant		ENST00000264159.11
ZRANB3	NM_001286568.2	c.360-54C>T		intron_variant
ZRANB3	NM_001286569.1	c.-1098-54C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZRANB3	ENST00000264159.11	c.360-54C>T		intron_variant		1	NM_032143.4	P4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28814 AN: 151830 Hom.: 3665 Cov.: 32

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

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.0743

Gnomad4 NFE exome AF: 0.0794

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.190 AC: 28862 AN: 151948 Hom.: 3676 Cov.: 32 AF XY: 0.193 AC XY: 14355 AN XY: 74274

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0956

Gnomad4 OTH AF: 0.198

Alfa AF: 0.134 Hom.: 739

Bravo AF: 0.205

Asia WGS AF: 0.296 AC: 1027 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	7.8
Dann	Benign	0.73

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: rs10496734; hg19: chr2-136107839;