1-151286458-C-T

Position:

• chr1-151286458-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020832.3(ZNF687):​c.167C>T​(p.Ala56Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF687 NM_020832.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.596

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07634443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF687	NM_020832.3	c.167C>T	p.Ala56Val	missense_variant	2/9	ENST00000336715.11	NP_065883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF687	ENST00000336715.11	c.167C>T	p.Ala56Val	missense_variant	2/9	1	NM_020832.3	ENSP00000336620.5
ZNF687	ENST00000324048.9	c.167C>T	p.Ala56Val	missense_variant	3/10	1		ENSP00000319829.5
ZNF687	ENST00000443959.1	c.194C>T	p.Ala65Val	missense_variant	2/2	1		ENSP00000395261.1
ZNF687	ENST00000449313.5	n.167C>T		non_coding_transcript_exon_variant	2/7	5		ENSP00000415286.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.167C>T (p.A56V) alteration is located in exon 2 (coding exon 1) of the ZNF687 gene. This alteration results from a C to T substitution at nucleotide position 167, causing the alanine (A) at amino acid position 56 to be replaced by a valine (V). 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	Benign	0.084
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.014	.;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.44	T;.;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.076	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	2.0	.;M;M
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.060	N;N;N
REVEL	Benign	0.027
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0010	.;B;B
Vest4		0.14, 0.17
MutPred		0.13		.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);
MVP		0.24
MPC		0.32
ClinPred		0.11	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.079

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr1-151258934;