chr12-133058771-A-C

Variant names:

• chr12-133058771-A-C
• NM_001289971.2:c.2056A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001289971.2(ZNF84):​c.2056A>C​(p.Ser686Arg) 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. 15/22 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: -0.881
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06522715).

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.2056A>C	p.Ser686Arg	missense	Exon 5 of 5	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.2056A>C	p.Ser686Arg	missense	Exon 5 of 5	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.2056A>C	p.Ser686Arg	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.2056A>C	p.Ser686Arg	missense	Exon 5 of 5	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.2056A>C	p.Ser686Arg	missense	Exon 5 of 5	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.2056A>C	p.Ser686Arg	missense	Exon 5 of 5	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

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	0.26
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.54	N
PhyloP100		-0.88
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.046
Sift	Uncertain	0.021	D
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.18
MutPred		0.40		Gain of catalytic residue at K681 (P = 0.0051)
MVP		0.12
ClinPred		0.12	T
GERP RS		1.5
Varity_R		0.11
gMVP		0.059
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr12-133635357;