12-133057883-C-T

Variant names:

• chr12-133057883-C-T
• NM_001289971.2:c.1168C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001289971.2(ZNF84):​c.1168C>T​(p.Leu390Phe) 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. 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: 0.934

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36240247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF84	NM_001289971.2	c.1168C>T	p.Leu390Phe	missense_variant	Exon 5 of 5	ENST00000539354.6	NP_001276900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF84	ENST00000539354.6	c.1168C>T	p.Leu390Phe	missense_variant	Exon 5 of 5	1	NM_001289971.2	ENSP00000445549.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1168C>T (p.L390F) alteration is located in exon 5 (coding exon 4) of the ZNF84 gene. This alteration results from a C to T substitution at nucleotide position 1168, causing the leucine (L) at amino acid position 390 to be replaced by a phenylalanine (F). 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	0.69
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;.;T;T
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.65	T;T;.;.
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.36	T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.0	M;.;M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Uncertain	0.35
Sift	Benign	0.099	T;T;T;T
Sift4G	Uncertain	0.051	T;T;T;T
Polyphen		1.0	D;.;D;D
Vest4		0.37
MutPred		0.70		Gain of relative solvent accessibility (P = 0.0522);.;Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP		0.33
ClinPred		0.97	D
GERP RS		2.5
Varity_R		0.25
gMVP		0.36

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: chr12-133634469;