10-124952367-T-C

Position:

• chr10-124952367-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359653.4(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 ENST00000359653.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ZRANB1	NM_017580.3	c.814+9060T>C		intron_variant		ENST00000359653.4	NP_060050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZRANB1	ENST00000359653.4	c.814+9060T>C		intron_variant		1	NM_017580.3	ENSP00000352676	P1

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

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0103

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.216

Alfa AF: 0.243 Hom.: 1127

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs67609008; hg19: chr10-126640936;