Variant 1-151286307-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020832.3(ZNF687):c.16A>G(p.Thr6Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,411,582 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. T6N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF687
NM_020832.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF687	NM_020832.3 link	c.16A>G	p.Thr6Ala	missense_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.16A>G	p.Thr6Ala	missense_variant	2/9	1	NM_020832.3	ENSP00000336620.5	Q8N1G0-1
ZNF687	ENST00000324048.9 link	c.16A>G	p.Thr6Ala	missense_variant	3/10	1		ENSP00000319829.5	Q8N1G0-1
ZNF687	ENST00000443959.1 link	c.43A>G	p.Thr15Ala	missense_variant	2/2	1		ENSP00000395261.1	A2A3Q2
ZNF687	ENST00000449313.5 link	n.16A>G		non_coding_transcript_exon_variant	2/7	5		ENSP00000415286.1	F8WCX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1411582

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698830

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.16A>G (p.T6A) alteration is located in exon 2 (coding exon 1) of the ZNF687 gene. This alteration results from a A to G substitution at nucleotide position 16, causing the threonine (T) at amino acid position 6 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

-0.0036

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;D;D

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

D;.;D

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

3.2

.;M;M

PrimateAI

Pathogenic

0.90

PROVEAN

Pathogenic

-4.8

D;D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

.;D;D

Vest4

0.41, 0.49

MutPred

0.33

.;Loss of phosphorylation at T6 (P = 0.0194);Loss of phosphorylation at T6 (P = 0.0194);

MVP

0.54

MPC

1.0

ClinPred

0.99

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.46

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over