rs1780061844

Variant names:

• chr7-6691188-G-C
• rs1780061844
• NM_016265.4:c.1754C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016265.4(ZNF12):​c.1754C>G​(p.Thr585Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,606 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: ZNF12 NM_016265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25
• Publications: 0 publications found

Genes affected

ZNF12 (HGNC:12902): (zinc finger protein 12) This gene is a member of the krueppel C2H2-type zinc-finger protein family and encodes a protein with eight C2H2-type zinc fingers and a KRAB domain. This nuclear protein is involved in developmental control of gene expression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

ENSG00000228010 (HGNC:):

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=0.072886795).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016265.4. 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
	ZNF12	NM_016265.4	MANE Select	c.1754C>G	p.Thr585Ser	missense	Exon 5 of 5	NP_057349.2	P17014-1
	ZNF12	NM_006956.3		c.1640C>G	p.Thr547Ser	missense	Exon 6 of 6	NP_008887.2	P17014-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF12	ENST00000405858.6	TSL:1 MANE Select	c.1754C>G	p.Thr585Ser	missense	Exon 5 of 5	ENSP00000385939.1	P17014-1
	ZNF12	ENST00000404360.5	TSL:1	c.1532C>G	p.Thr511Ser	missense	Exon 5 of 5	ENSP00000384405.1	P17014-4
	ZNF12	ENST00000342651.9	TSL:2	c.1640C>G	p.Thr547Ser	missense	Exon 6 of 6	ENSP00000344745.5	P17014-5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151800 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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461806 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727190

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

American (AMR) AF: 0.00 AC: 0 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

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

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111976

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151800 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74118

African (AFR) AF: 0.00 AC: 0 AN: 41276

American (AMR) AF: 0.00 AC: 0 AN: 15256

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67940

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

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

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	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.14	T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.45	N
PhyloP100		1.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.020
Sift	Benign	0.12	T
Sift4G	Benign	0.23	T
Polyphen		0.12	B
Vest4		0.14
MutPred		0.43		Gain of disorder (P = 0.0355)
MVP		0.10
MPC		0.24
ClinPred		0.14	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.057
gMVP		0.049
Mutation Taster		=93/7	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: rs1780061844; hg19: chr7-6730819;