chr1-151289853-CC-GT

Variant names:

• chr1-151289853-CC-GT
• NM_020832.3:c.2810_2811delCCinsGT
• ZNF687 p.Pro937Arg

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PS1_Moderate

The NM_020832.3(ZNF687):​c.2810_2811delCCinsGT​(p.Pro937Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely pathogenic in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P937L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF687 NM_020832.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PS1: Transcript NM_020832.3 (ZNF687) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in ClinVar.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF687	NM_020832.3	MANE Select	c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	NP_065883.1	Q8N1G0-1
	ZNF687	NM_001304763.2		c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	NP_001291692.1	Q8N1G0-1
	ZNF687	NM_001304764.2		c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	NP_001291693.1	Q8N1G0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF687	ENST00000336715.11	TSL:1 MANE Select	c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	ENSP00000336620.5	Q8N1G0-1
	ZNF687	ENST00000324048.9	TSL:1	c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	ENSP00000319829.5	Q8N1G0-1
	ZNF687	ENST00000853018.1		c.2810_2811delCCinsGT	p.Pro937Arg	missense	N/A	ENSP00000523077.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8

Splicing

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.

Other links and lift over

hg19: chr1-151262329;