chr10-124952367-T-C

Variant names:

• chr10-124952367-T-C
• rs67609008
• NM_017580.3:c.814+9060T>C

Variant summary

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

The NM_017580.3(ZRANB1):​c.814+9060T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,100 control chromosomes in the GnomAD database, including 3,573 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 (3573 hom., cov: 32)
• Consequence: ZRANB1 NM_017580.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 8 publications found

Genes affected

ZRANB1 (HGNC:18224): (zinc finger RANBP2-type containing 1) Enables K63-linked polyubiquitin modification-dependent protein binding activity and thiol-dependent deubiquitinase. Involved in several processes, including positive regulation of Wnt signaling pathway; protein deubiquitination; and regulation of cell morphogenesis. Located in cytosol 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZRANB1	NM_017580.3	c.814+9060T>C		intron_variant	Intron 1 of 8	ENST00000359653.4	NP_060050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZRANB1	ENST00000359653.4	c.814+9060T>C		intron_variant	Intron 1 of 8	1	NM_017580.3	ENSP00000352676.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28862 AN: 151982 Hom.: 3576 Cov.: 32

Gnomad AFR AF: 0.0545

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0103

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.190 AC: 28858 AN: 152100 Hom.: 3573 Cov.: 32 AF XY: 0.186 AC XY: 13834 AN XY: 74342

African (AFR) AF: 0.0544 AC: 2258 AN: 41516

American (AMR) AF: 0.192 AC: 2931 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5158

South Asian (SAS) AF: 0.306 AC: 1473 AN: 4806

European-Finnish (FIN) AF: 0.173 AC: 1837 AN: 10594

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.275 AC: 18673 AN: 67960

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.254 Hom.: 2217

Bravo AF: 0.182

Asia WGS AF: 0.119 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		1.3
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

Other links and lift over

dbSNP: rs67609008; hg19: chr10-126640936;