17-32366681-C-A

Position:

• chr17-32366681-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001098507.2(ZNF207):​c.845C>A​(p.Thr282Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF207 NM_001098507.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.73

Genes affected

ZNF207 (HGNC:12998): (zinc finger protein 207) Enables microtubule binding activity. Involved in several processes, including mitotic nuclear division; mitotic spindle assembly checkpoint signaling; and protein stabilization. Located in kinetochore; nuclear lumen; and spindle matrix. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3093658).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF207	NM_001098507.2	c.845C>A	p.Thr282Lys	missense_variant	9/12	ENST00000394670.9	NP_001091977.1
ZNF207	NM_003457.4	c.797C>A	p.Thr266Lys	missense_variant	8/11		NP_003448.1
ZNF207	NM_001032293.3	c.829-1091C>A		intron_variant			NP_001027464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF207	ENST00000394670.9	c.845C>A	p.Thr282Lys	missense_variant	9/12	1	NM_001098507.2	ENSP00000378165

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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

Jun 09, 2022

The c.845C>A (p.T282K) alteration is located in exon 9 (coding exon 9) of the ZNF207 gene. This alteration results from a C to A substitution at nucleotide position 845, causing the threonine (T) at amino acid position 282 to be replaced by a lysine (K). 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	0.29
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	26
DANN	Benign	0.86
DEOGEN2	Benign	0.015	.;T;T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.31	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.79	N;.;.;.
REVEL	Benign	0.14
Sift	Benign	0.19	T;.;.;.
Sift4G	Benign	0.52	T;T;T;T
Polyphen		0.36	.;B;.;.
Vest4		0.55
MutPred		0.33		.;Gain of ubiquitination at T266 (P = 0.0037);.;.;
MVP		0.53
MPC		0.43
ClinPred		0.65	D
GERP RS		6.1
Varity_R		0.050
gMVP		0.37

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: chr17-30693700;