chr7-6691323-C-T

Variant names:

• chr7-6691323-C-T
• rs779902364
• NM_016265.4:c.1619G>A

Variant summary

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

The NM_016265.4(ZNF12):​c.1619G>A​(p.Arg540Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,611,724 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R540W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: ZNF12 NM_016265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.73
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023217976).

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.1619G>A	p.Arg540Gln	missense	Exon 5 of 5	NP_057349.2	P17014-1
	ZNF12	NM_006956.3		c.1505G>A	p.Arg502Gln	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.1619G>A	p.Arg540Gln	missense	Exon 5 of 5	ENSP00000385939.1	P17014-1
	ZNF12	ENST00000404360.5	TSL:1	c.1397G>A	p.Arg466Gln	missense	Exon 5 of 5	ENSP00000384405.1	P17014-4
	ZNF12	ENST00000342651.9	TSL:2	c.1505G>A	p.Arg502Gln	missense	Exon 6 of 6	ENSP00000344745.5	P17014-5

Frequencies

GnomAD3 genomes AF: 0.0000531 AC: 8 AN: 150790 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000976

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: 0.0000592

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000200 AC: 5 AN: 249634 AF XY: 0.0000148

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000404 AC: 59 AN: 1460934 Hom.: 0 Cov.: 31 AF XY: 0.0000372 AC XY: 27 AN XY: 726736

African (AFR) AF: 0.0000896 AC: 3 AN: 33478

American (AMR) AF: 0.0000225 AC: 1 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39670

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85998

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000423 AC: 47 AN: 1111640

Other (OTH) AF: 0.0000497 AC: 3 AN: 60354

GnomAD4 genome AF: 0.0000531 AC: 8 AN: 150790 Hom.: 0 Cov.: 33 AF XY: 0.0000272 AC XY: 2 AN XY: 73610

African (AFR) AF: 0.0000976 AC: 4 AN: 41000

American (AMR) AF: 0.00 AC: 0 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.00 AC: 0 AN: 5086

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67620

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000604

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000247 AC: 3

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	0.079
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.7
DANN	Benign	0.68
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.000050	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.56	N
PhyloP100		-2.7
PrimateAI	Benign	0.27	T
PROVEAN	Benign	3.2	N
REVEL	Benign	0.032
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0070	B
Vest4		0.12
MVP		0.16
MPC		0.27
ClinPred		0.013	T
GERP RS		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.012
gMVP		0.14
Mutation Taster		=96/4	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: rs779902364; hg19: chr7-6730954; COSMIC: COSV61243751;