Menu
GeneBe

10-124983198-G-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017580.3(ZRANB1):c.1572G>T(p.Thr524=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000558 in 1,613,714 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

ZRANB1
NM_017580.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.169
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 10-124983198-G-T is Benign according to our data. Variant chr10-124983198-G-T is described in ClinVar as [Benign]. Clinvar id is 722721.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.169 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZRANB1NM_017580.3 linkuse as main transcriptc.1572G>T p.Thr524= synonymous_variant 7/9 ENST00000359653.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZRANB1ENST00000359653.4 linkuse as main transcriptc.1572G>T p.Thr524= synonymous_variant 7/91 NM_017580.3 P1
ZRANB1ENST00000471421.1 linkuse as main transcriptn.443G>T non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00248
AC:
378
AN:
152146
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00807
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000714
AC:
179
AN:
250750
Hom.:
2
AF XY:
0.000590
AC XY:
80
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.00698
Gnomad AMR exome
AF:
0.000986
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.000655
GnomAD4 exome
AF:
0.000356
AC:
520
AN:
1461450
Hom.:
1
Cov.:
31
AF XY:
0.000337
AC XY:
245
AN XY:
727026
show subpopulations
Gnomad4 AFR exome
AF:
0.00774
Gnomad4 AMR exome
AF:
0.00108
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000134
Gnomad4 OTH exome
AF:
0.000861
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00250
AC:
380
AN:
152264
Hom.:
3
Cov.:
32
AF XY:
0.00266
AC XY:
198
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00809
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00118
Hom.:
2
Bravo
AF:
0.00255
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000296

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
3.5
Dann
Benign
0.81

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75293113; hg19: chr10-126671767; COSMIC: COSV61478648; COSMIC: COSV61478648; API