Genetic Variant ZRANB3:c.2352+149T>A (chr2-135218928-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The NM_032143.4(ZRANB3):c.2352+149T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. 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: not found (cov: 32)

Consequence

ZRANB3
NM_032143.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09

Publications

0 publications found

Variant links:

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 links:

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new If you want to explore the variant's impact on the transcript NM_032143.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 points.

PM2

Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	NM_032143.4	MANE Select	c.2352+149T>A	intron	N/A	NP_115519.2	Q5FWF4-1
ZRANB3	NM_001286568.2		c.2346+149T>A	intron	N/A	NP_001273497.1	Q5FWF4-3
ZRANB3	NM_001286569.1		c.990+149T>A	intron	N/A	NP_001273498.1	F5GYN7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZRANB3	ENST00000264159.11	TSL:1 MANE Select	c.2352+149T>A	intron	N/A	ENSP00000264159.6	Q5FWF4-1
ZRANB3	ENST00000401392.5	TSL:1	c.2346+149T>A	intron	N/A	ENSP00000383979.1	Q5FWF4-3
ZRANB3	ENST00000536680.5	TSL:1	c.990+149T>A	intron	N/A	ENSP00000441320.2	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 2 sources Large-scale international reference populations
GnomAD3 genomes					32
GnomAD4 genome					32
Local & regional cohorts 1 source Population-specific and national genomic databases
ToMMo 61KJPN (+60KJPN MNV)	0.00000800	1	0	122800

Showing 3 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	8.9
BayesDel_noAF	Benign	-	-0.84
CADD	Benign	-	3.0
DANN	Benign	-	0.37
GPN-Star LLR	N/A	-	-1.1
GPN-Star score	N/A	-	1.1
PhyloP100	Benign	-	1.1

Showing 7 of 7 scores

Splicing Scores

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

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over