rs1375131

Positions:

• chr2-135197227-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.*3115A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,160 control chromosomes in the GnomAD database, including 33,633 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 0.61 (33633 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ZRANB3 NM_032143.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZRANB3	NM_032143.4	c.*3115A>G		3_prime_UTR_variant	21/21	ENST00000264159.11	NP_115519.2
ZRANB3	NM_001286568.2	c.*3115A>G		3_prime_UTR_variant	21/21		NP_001273497.1
ZRANB3	NM_001286569.1	c.*3115A>G		3_prime_UTR_variant	22/22		NP_001273498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB3	ENST00000264159.11	c.*3115A>G		3_prime_UTR_variant	21/21	1	NM_032143.4	ENSP00000264159	P4

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92775 AN: 152042 Hom.: 33567 Cov.: 32

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.779

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.706

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.611 AC: 92905 AN: 152160 Hom.: 33633 Cov.: 32 AF XY: 0.625 AC XY: 46520 AN XY: 74402

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.779

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.710

Alfa AF: 0.487 Hom.: 12400

Bravo AF: 0.649

Asia WGS AF: 0.923 AC: 3209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1375131; hg19: chr2-135954797;