12-133057133-C-G

Variant names:

• chr12-133057133-C-G
• rs267603389
• NM_001289971.2:c.418C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001289971.2(ZNF84):​c.418C>G​(p.His140Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF84 NM_001289971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.163
• Publications: 0 publications found

Genes affected

ZNF84 (HGNC:13159): (zinc finger protein 84) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07875165).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF84	NM_001289971.2	MANE Select	c.418C>G	p.His140Asp	missense	Exon 5 of 5	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.418C>G	p.His140Asp	missense	Exon 5 of 5	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.418C>G	p.His140Asp	missense	Exon 5 of 5	NP_001276901.1	P51523

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF84	ENST00000539354.6	TSL:1 MANE Select	c.418C>G	p.His140Asp	missense	Exon 5 of 5	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.418C>G	p.His140Asp	missense	Exon 5 of 5	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.418C>G	p.His140Asp	missense	Exon 5 of 5	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.035	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.16
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.079
Sift	Benign	0.45	T
Sift4G	Benign	0.21	T
Polyphen		0.59	P
Vest4		0.33
MutPred		0.31		Gain of catalytic residue at L141 (P = 0)
MVP		0.11
ClinPred		0.15	T
GERP RS		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.062
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs267603389; hg19: chr12-133633719;