7-100071612-T-A

Position:

• chr7-100071612-T-A

Variant summary

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

The NM_032924.5(ZNF3):​c.872A>T​(p.Lys291Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF3 NM_032924.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.93

Genes affected

ZNF3 (HGNC:13089): (zinc finger protein 3) Enables identical protein binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF3 (HGNC:):

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
ZNF3	NM_032924.5	c.872A>T	p.Lys291Met	missense_variant	6/6	ENST00000299667.9	NP_116313.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF3	ENST00000299667.9	c.872A>T	p.Lys291Met	missense_variant	6/6	1	NM_032924.5	ENSP00000299667.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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 22, 2024

The c.872A>T (p.K291M) alteration is located in exon 6 (coding exon 4) of the ZNF3 gene. This alteration results from a A to T substitution at nucleotide position 872, causing the lysine (K) at amino acid position 291 to be replaced by a methionine (M). 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	Pathogenic	0.68
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T;T;T
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.73	.;T;.
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-5.2	D;D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.50
MutPred		0.45		Loss of methylation at K291 (P = 0.0027);Loss of methylation at K291 (P = 0.0027);Loss of methylation at K291 (P = 0.0027);
MVP		0.67
MPC		1.2
ClinPred		1.0	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.71
gMVP		0.18

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: chr7-99669235;