NM_001289971.2:c.1247C>T

Variant names:

• chr12-133057962-C-T
• rs1414551724
• NM_001289971.2:c.1247C>T

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.1247C>T​(p.Ser416Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,642 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 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ZNF84 NM_001289971.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.242
• 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=0.25686044).

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.1247C>T	p.Ser416Leu	missense	Exon 5 of 5	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.1247C>T	p.Ser416Leu	missense	Exon 5 of 5	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.1247C>T	p.Ser416Leu	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.1247C>T	p.Ser416Leu	missense	Exon 5 of 5	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.1247C>T	p.Ser416Leu	missense	Exon 5 of 5	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.1247C>T	p.Ser416Leu	missense	Exon 5 of 5	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151860 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461782 Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 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: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

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

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112008

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151860 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74140

African (AFR) AF: 0.0000242 AC: 1 AN: 41330

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Pathogenic	0.81
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.24
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.13
Sift	Benign	0.035	D
Sift4G	Benign	0.22	T
Polyphen		0.98	D
Vest4		0.36
MutPred		0.55		Gain of catalytic residue at R413 (P = 0.0038)
MVP		0.22
ClinPred		0.87	D
GERP RS		2.5
Varity_R		0.14
gMVP		0.23
Mutation Taster		=90/10	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: rs1414551724; hg19: chr12-133634548;