NM_001289971.2:c.965A>G

Variant names:

• chr12-133057680-A-G
• rs113644344
• NM_001289971.2:c.965A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001289971.2(ZNF84):​c.965A>G​(p.Asn322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: ZNF84 NM_001289971.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.35
• 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.017231494).
• BP6: Variant 12-133057680-A-G is Benign according to our data. Variant chr12-133057680-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2295713.Status of the report is criteria_provided_single_submitter, 1 stars.

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.965A>G	p.Asn322Ser	missense	Exon 5 of 5	NP_001276900.1	P51523
	ZNF84	NM_001127372.3		c.965A>G	p.Asn322Ser	missense	Exon 5 of 5	NP_001120844.1	P51523
	ZNF84	NM_001289972.2		c.965A>G	p.Asn322Ser	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.965A>G	p.Asn322Ser	missense	Exon 5 of 5	ENSP00000445549.1	P51523
	ZNF84	ENST00000327668.11	TSL:1	c.965A>G	p.Asn322Ser	missense	Exon 5 of 5	ENSP00000331465.7	P51523
	ZNF84	ENST00000392319.6	TSL:1	c.965A>G	p.Asn322Ser	missense	Exon 5 of 5	ENSP00000376133.2	P51523

Frequencies

GnomAD3 genomes AF: 0.00000665 AC: 1 AN: 150382 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1461832 Hom.: 0 Cov.: 35 AF XY: 0.0000110 AC XY: 8 AN XY: 727212

African (AFR) AF: 0.000120 AC: 4 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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: 53418

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

European-Non Finnish (NFE) AF: 0.00000629 AC: 7 AN: 1112000

Other (OTH) AF: 0.000248 AC: 15 AN: 60392

GnomAD4 genome AF: 0.00000665 AC: 1 AN: 150382 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73398

African (AFR) AF: 0.00 AC: 0 AN: 40904

American (AMR) AF: 0.00 AC: 0 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 4958

South Asian (SAS) AF: 0.00 AC: 0 AN: 4726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67472

Other (OTH) AF: 0.00 AC: 0 AN: 2074

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.051
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.47
DEOGEN2	Benign	0.020	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.017	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.56	N
PhyloP100		-3.4
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.011
Sift	Benign	0.54	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.042
MutPred		0.33		Gain of catalytic residue at G320 (P = 0.0055)
MVP		0.055
ClinPred		0.028	T
GERP RS		-4.9
Varity_R		0.014
gMVP		0.068
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: rs113644344; hg19: chr12-133634266;