NM_032143.4:c.2352+149T>C

Variant names:

• chr2-135218928-A-G
• rs4954228
• NM_032143.4:c.2352+149T>C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_032143.4(ZRANB3):c.2352+149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.177 (AC=97,154) in the gnomAD database across 549,536 control chromosomes, including 15,622 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.597. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (9188 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6434 hom.)
• Consequence: ZRANB3 NM_032143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 4 publications found

Genes affected

ZRANB3 (HGNC:25249): (zinc finger RANBP2-type containing 3) Enables ATP-dependent DNA/DNA annealing activity; DNA endonuclease activity; and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in DNA repair; replication fork reversal; and response to UV. Located in nuclear replication fork and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5974 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_032143.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ZRANB3 NM_032143.4	MANE Select	c.2352+149T>C	intron	Intron 16 of 20	Prot: NP_115519.2 UniProt:
	ZRANB3 NM_001286568.2		c.2346+149T>C	intron	Intron 16 of 20	Prot: NP_001273497.1 UniProt:
	ZRANB3 NM_001286569.1		c.990+149T>C	intron	Intron 17 of 21	Prot: NP_001273498.1 UniProt:

ZRANB3 NM_032143.4

MANE Select

HGVSc / HGVSpc.2352+149T>C

Exon rankIntron 16 of 20

intron

Prot: NP_115519.2UniProt: Q5FWF4-1

ZRANB3 NM_001286568.2

HGVSc / HGVSpc.2346+149T>C

Exon rankIntron 16 of 20

intron

Prot: NP_001273497.1UniProt: Q5FWF4-3

ZRANB3 NM_001286569.1

HGVSc / HGVSpc.990+149T>C

Exon rankIntron 17 of 21

intron

Prot: NP_001273498.1UniProt: F5GYN7

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ZRANB3 ENST00000264159.11	TSL:1MANE Select	c.2352+149T>C	intron	Intron 16 of 20	Prot: ENSP00000264159.6 UniProt:
	ZRANB3 ENST00000401392.5	TSL:1	c.2346+149T>C	intron	Intron 16 of 20	Prot: ENSP00000383979.1 UniProt:
	ZRANB3 ENST00000536680.5	TSL:1	c.990+149T>C	intron	Intron 17 of 21	Prot: ENSP00000441320.2 UniProt:

ZRANB3 ENST00000264159.11

TSL:1MANE Select

HGVSc / HGVSpc.2352+149T>C

Exon rankIntron 16 of 20

intron

Prot: ENSP00000264159.6UniProt: Q5FWF4-1

ZRANB3 ENST00000401392.5

TSL:1

HGVSc / HGVSpc.2346+149T>C

Exon rankIntron 16 of 20

intron

Prot: ENSP00000383979.1UniProt: Q5FWF4-3

ZRANB3 ENST00000536680.5

TSL:1

HGVSc / HGVSpc.990+149T>C

Exon rankIntron 17 of 21

intron

Prot: ENSP00000441320.2UniProt: F5GYN7

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 5 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.268	AC:40813	Hom:9160	AN:152060	Cov:32
GnomAD4 exome	AF: 0.142	AC:56262	Hom:6434	AN:397358	Cov:
GnomAD4 genome	AF: 0.269	AC:40892	Hom:9188	AN:152178	Cov:32
TOPMed (Bravo)	AF: 0.294	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.169	AC:18496	Hom:2885	AN:109516	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.283	AC:662	Hom:121	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.201	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.0767	AC:23	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.313	AC:1088	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.205	AC:1480	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.239	AC:42	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.218	AC:26733	Hom:2916	AN:122800	Cov:
Turkish Variome	AF: 0.248	AC:383	Hom:56	AN:1546	Cov:
UK10K	AF: 0.0754	AC:570	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.208	AC:1864	Hom:184	AN:8960	Cov:

Showing 15 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.0847	3845	45378	0.0798	6333	79324

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Uncertain	11
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.44
GPN-Star LLR	N/A	1.4
GPN-Star score	N/A	-1.4
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	1.1

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs4954228;

hg19: chr2-135976498;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar