16-3232540-A-G

Position:

• chr16-3232540-A-G

Variant summary

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

The NM_198088.3(ZNF200):​c.347T>C​(p.Val116Ala) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF200 NM_198088.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34

Genes affected

ZNF200 (HGNC:12993): (zinc finger protein 200) Predicted to enable metal ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09994018).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF200	NM_198088.3	c.347T>C	p.Val116Ala	missense_variant	4/5	ENST00000414144.7	NP_932354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF200	ENST00000414144.7	c.347T>C	p.Val116Ala	missense_variant	4/5	1	NM_198088.3	ENSP00000405786	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

May 26, 2024

The c.347T>C (p.V116A) alteration is located in exon 4 (coding exon 3) of the ZNF200 gene. This alteration results from a T to C substitution at nucleotide position 347, causing the valine (V) at amino acid position 116 to be replaced by an alanine (A). 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	0.45
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.057	.;T;.;T;.;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.32	T;.;.;T;.;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.10	T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	.;M;M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N;N;N;N;.
REVEL	Benign	0.044
Sift	Uncertain	0.0020	D;D;D;D;D;.
Sift4G	Benign	0.10	T;T;T;T;T;T
Polyphen		0.0030	B;B;.;B;.;.
Vest4		0.090
MutPred		0.56		.;Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);Gain of sheet (P = 0.1451);
MVP		0.24
MPC		0.0078
ClinPred		0.11	T
GERP RS		1.1
Varity_R		0.068
gMVP		0.043

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-3282540;