1-151289853-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM5BP4_StrongBS2

The NM_020832.3(ZNF687):c.2810C>T(p.Pro937Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,568,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P937R) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF687
NM_020832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 1.81

Publications

14 publications found

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 Gene-Disease associations (from GenCC):

Paget disease of bone 6
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ZNF687 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020832.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chr1-151289853-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 222987.

BP4

Computational evidence support a benign effect (MetaRNN=0.017930776).

BS2

High AC in GnomAd4 at 24 Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020832.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF687	NM_020832.3	MANE Select	c.2810C>T	p.Pro937Leu	missense	Exon 6 of 9	NP_065883.1	Q8N1G0-1
ZNF687	NM_001304763.2		c.2810C>T	p.Pro937Leu	missense	Exon 7 of 10	NP_001291692.1	Q8N1G0-1
ZNF687	NM_001304764.2		c.2810C>T	p.Pro937Leu	missense	Exon 6 of 9	NP_001291693.1	Q8N1G0-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF687	ENST00000336715.11	TSL:1 MANE Select	c.2810C>T	p.Pro937Leu	missense	Exon 6 of 9	ENSP00000336620.5	Q8N1G0-1
ZNF687	ENST00000324048.9	TSL:1	c.2810C>T	p.Pro937Leu	missense	Exon 7 of 10	ENSP00000319829.5	Q8N1G0-1
ZNF687	ENST00000853018.1		c.2810C>T	p.Pro937Leu	missense	Exon 6 of 9	ENSP00000523077.1

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000119

AC:

AN:

175820

AF XY:

0.000117

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.0000375

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000532

Gnomad FIN exome

AF:

0.000122

Gnomad NFE exome

AF:

0.0000694

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

158

AN:

1415828

Hom.:

Cov.:

AF XY:

0.000106

AC XY:

AN XY:

700252

show subpopulations

African (AFR)

AF:

0.000248

AC:

AN:

32288

American (AMR)

AF:

0.0000530

AC:

AN:

37764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25314

East Asian (EAS)

AF:

0.000189

AC:

AN:

37052

South Asian (SAS)

AF:

0.000296

AC:

AN:

81136

European-Finnish (FIN)

AF:

0.0000998

AC:

AN:

50106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0000947

AC:

103

AN:

1087836

Other (OTH)

AF:

0.000154

AC:

AN:

58626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000158

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41588

American (AMR)

AF:

0.000131

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Paget disease of bone 6 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.023

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.62

M_CAP

Benign

0.014

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.39

MutationAssessor

Benign

0.69

PhyloP100

1.8

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.76

REVEL

Benign

0.079

Sift

Uncertain

0.0090

Sift4G

Benign

0.073

Varity_R

0.063

gMVP

0.45

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over