17-32369656-C-T

Position:

• chr17-32369656-C-T

Variant summary

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

The NM_001098507.2(ZNF207):​c.1382C>T​(p.Pro461Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000763 in 1,442,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: ZNF207 NM_001098507.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12

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 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
ZNF207	NM_001098507.2	c.1382C>T	p.Pro461Leu	missense_variant	12/12	ENST00000394670.9	NP_001091977.1
ZNF207	NM_003457.4	c.1334C>T	p.Pro445Leu	missense_variant	11/11		NP_003448.1
ZNF207	NM_001032293.3	c.1289C>T	p.Pro430Leu	missense_variant	11/11		NP_001027464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF207	ENST00000394670.9	c.1382C>T	p.Pro461Leu	missense_variant	12/12	1	NM_001098507.2	ENSP00000378165

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000763 AC: 11 AN: 1442106 Hom.: 0 Cov.: 32 AF XY: 0.00000839 AC XY: 6 AN XY: 715522

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000907

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

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

Nov 14, 2023

The c.1382C>T (p.P461L) alteration is located in exon 12 (coding exon 12) of the ZNF207 gene. This alteration results from a C to T substitution at nucleotide position 1382, causing the proline (P) at amino acid position 461 to be replaced by a leucine (L). 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	.;T;.;T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.52	D;D;D;D;D
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	1.9	.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.8	D;N;N;N;.
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;T;T;.
Sift4G	Benign	0.13	T;D;D;T;T
Polyphen		1.0	.;D;D;.;.
Vest4		0.70
MutPred		0.16		.;Loss of catalytic residue at P444 (P = 0.0131);.;.;.;
MVP		0.77
MPC		0.36
ClinPred		0.99	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.51
gMVP		0.39

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

LitVar

Other links and lift over

dbSNP: rs760182750; hg19: chr17-30696675;