Variant 1-151286567-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020832.3(ZNF687):c.276C>T(p.Pro92Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,614,088 control chromosomes in the GnomAD database, including 10,830 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1103 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9727 hom. )

Consequence

ZNF687
NM_020832.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.48

Variant links:

Genes affected

ZNF687 (HGNC:29277): (zinc finger protein 687) This gene encodes C2H2 zinc finger protein. The encoded protein may play a role in bone differentiation and development. Mutations in this gene are the cause of Paget disease of bone-6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ZNF687 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-151286567-C-T is Benign according to our data. Variant chr1-151286567-C-T is described in ClinVar as [Benign]. Clinvar id is 1611976.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.48 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF687	NM_020832.3 link	c.276C>T	p.Pro92Pro	synonymous_variant	2/9	ENST00000336715.11	NP_065883.1	Q8N1G0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF687	ENST00000336715.11 link	c.276C>T	p.Pro92Pro	synonymous_variant	2/9	1	NM_020832.3	ENSP00000336620.5	Q8N1G0-1
ZNF687	ENST00000324048.9 link	c.276C>T	p.Pro92Pro	synonymous_variant	3/10	1		ENSP00000319829.5	Q8N1G0-1
ZNF687	ENST00000443959.1 link	c.303C>T	p.Pro101Pro	synonymous_variant	2/2	1		ENSP00000395261.1	A2A3Q2
ZNF687	ENST00000449313.5 link	n.276C>T		non_coding_transcript_exon_variant	2/7	5		ENSP00000415286.1	F8WCX2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17866

AN:

152098

Hom.:

1101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.0588

Gnomad SAS

AF:

0.0904

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.113

AC:

28441

AN:

250952

Hom.:

1785

AF XY:

0.114

AC XY:

15418

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.0548

Gnomad SAS exome

AF:

0.0971

Gnomad FIN exome

AF:

0.110

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.134

GnomAD4 exome

AF:

0.113

AC:

164847

AN:

1461874

Hom.:

9727

Cov.:

AF XY:

0.113

AC XY:

82335

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.0958

Gnomad4 FIN exome

AF:

0.108

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.117

AC:

17880

AN:

152214

Hom.:

1103

Cov.:

AF XY:

0.119

AC XY:

8870

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.0589

Gnomad4 SAS

AF:

0.0909

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.125

Hom.:

2120

Bravo

AF:

0.122

Asia WGS

AF:

0.0870

AC:

302

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.126

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ZNF687-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.20

DANN

Benign

0.69

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over