17-32369640-C-T

Position:

• chr17-32369640-C-T

Variant summary

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

The NM_001098507.2(ZNF207):​c.1366C>T​(p.Pro456Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,430,064 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: 0.0000021 (0 hom.)
• Consequence: ZNF207 NM_001098507.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

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.1366C>T	p.Pro456Ser	missense_variant	12/12	ENST00000394670.9	NP_001091977.1
ZNF207	NM_003457.4	c.1318C>T	p.Pro440Ser	missense_variant	11/11		NP_003448.1
ZNF207	NM_001032293.3	c.1273C>T	p.Pro425Ser	missense_variant	11/11		NP_001027464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF207	ENST00000394670.9	c.1366C>T	p.Pro456Ser	missense_variant	12/12	1	NM_001098507.2	ENSP00000378165

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1430064 Hom.: 0 Cov.: 32 AF XY: 0.00000282 AC XY: 2 AN XY: 708614

Gnomad4 AFR exome AF: 0.0000620

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 06, 2023

The c.1366C>T (p.P456S) 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 1366, causing the proline (P) at amino acid position 456 to be replaced by a serine (S). 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	0.094
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	.;T;.;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.44	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	.;M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.1	D;N;.;.;.
REVEL	Benign	0.16
Sift	Uncertain	0.016	D;T;.;.;.
Sift4G	Uncertain	0.049	D;D;D;D;T
Polyphen		0.87	.;P;P;.;.
Vest4		0.61
MutPred		0.23		.;Gain of glycosylation at P440 (P = 0.0273);.;.;.;
MVP		0.55
MPC		0.36
ClinPred		0.98	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.30
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1905375012; hg19: chr17-30696659;