Variant 1-151286637-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_020832.3(ZNF687):c.346G>A(p.Gly116Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00636 in 1,614,190 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 57 hom. )

Consequence

ZNF687
NM_020832.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.20

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031077862).

BP6

Variant 1-151286637-G-A is Benign according to our data. Variant chr1-151286637-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 779222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 667 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF687	NM_020832.3 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	2/9	ENST00000336715.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF687	ENST00000336715.11 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	2/9	1	NM_020832.3	P1	Q8N1G0-1
ZNF687	ENST00000324048.9 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant	3/10	1		P1	Q8N1G0-1
ZNF687	ENST00000443959.1 linkuse as main transcript	c.373G>A	p.Gly125Arg	missense_variant	2/2	1
ZNF687	ENST00000449313.5 linkuse as main transcript	c.346G>A	p.Gly116Arg	missense_variant, NMD_transcript_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00953

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00690

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00513

AC:

1290

AN:

251306

Hom.:

AF XY:

0.00564

AC XY:

766

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00836

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00768

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00657

AC:

9602

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00657

AC XY:

4778

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00825

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00739

Gnomad4 OTH exome

AF:

0.00551

GnomAD4 genome

AF:

0.00438

AC:

667

AN:

152326

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

317

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00975

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00690

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00588

Hom.:

Bravo

AF:

0.00416

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00530

AC:

643

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00660

EpiControl

AF:

0.00705

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	ZNF687: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 07, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.71

T;.;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0050

D;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.13

.;B;B

Vest4

0.14, 0.13

MutPred

0.17

.;Gain of methylation at K114 (P = 0.0489);Gain of methylation at K114 (P = 0.0489);

MVP

0.16

MPC

0.38

ClinPred

0.018

GERP RS

4.3

Varity_R

0.13

gMVP

0.093

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