chr12-133058139-T-G

Variant names:

• chr12-133058139-T-G
• rs1007369699
• NM_001289971.2:c.1424T>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.1424T>G​(p.Val475Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: ZNF84 NM_001289971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.463
• 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=0.16809374).

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.1424T>G	p.Val475Gly	missense	Exon 5 of 5	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.1424T>G	p.Val475Gly	missense	Exon 5 of 5	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.1424T>G	p.Val475Gly	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.1424T>G	p.Val475Gly	missense	Exon 5 of 5	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.1424T>G	p.Val475Gly	missense	Exon 5 of 5	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.1424T>G	p.Val475Gly	missense	Exon 5 of 5	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152152 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000725 AC: 106 AN: 1461704 Hom.: 0 Cov.: 36 AF XY: 0.0000743 AC XY: 54 AN XY: 727138

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000872 AC: 97 AN: 1112002

Other (OTH) AF: 0.0000993 AC: 6 AN: 60394

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152152 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.0000654 AC: 1 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.46
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.11
Sift	Benign	0.15	T
Sift4G	Pathogenic	0.0010	D
Polyphen		0.63	P
Vest4		0.28
MutPred		0.34		Gain of catalytic residue at R479 (P = 0.0025)
MVP		0.15
ClinPred		0.83	D
GERP RS		2.8
Varity_R		0.49
gMVP		0.19
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

dbSNP: rs1007369699; hg19: chr12-133634725;