ENST00000401392.5:c.-185G>A

Variant names:

• chr2-135530703-C-T
• rs3806502
• ENST00000401392.5:c.-185G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000401392.5(ZRANB3):​c.-185G>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 ENST00000401392.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401392.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	NM_032143.4	MANE Select	c.-8+424G>A		intron	N/A	NP_115519.2	Q5FWF4-1
	ZRANB3	NM_001286569.1		c.-1670G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	NP_001273498.1	F5GYN7
	ZRANB3	NM_001286569.1		c.-1670G>A		5_prime_UTR	Exon 1 of 22	NP_001273498.1	F5GYN7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZRANB3	ENST00000401392.5	TSL:1	c.-185G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000383979.1	Q5FWF4-3
	ZRANB3	ENST00000536680.5	TSL:1	c.-1670G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 22	ENSP00000441320.2	F5GYN7
	ZRANB3	ENST00000401392.5	TSL:1	c.-185G>A		5_prime_UTR	Exon 1 of 21	ENSP00000383979.1	Q5FWF4-3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.100 AC: 2 AN: 20

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.652 AC: 27041 AN: 41466

American (AMR) AF: 0.323 AC: 4933 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 850 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1145 AN: 5178

South Asian (SAS) AF: 0.380 AC: 1830 AN: 4822

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10610

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8839 AN: 68004

Other (OTH) AF: 0.287 AC: 607 AN: 2114

Alfa AF: 0.204 Hom.: 15196

Bravo AF: 0.333

Asia WGS AF: 0.335 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.8
DANN	Benign	0.75
PhyloP100		-0.20
PromoterAI		0.023	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3806502;

hg19: chr2-136288273;