7-6692278-A-G

Position:

• chr7-6692278-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016265.4(ZNF12):​c.664T>C​(p.Cys222Arg) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF12 NM_016265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.763

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4	c.664T>C	p.Cys222Arg	missense_variant	5/5	ENST00000405858.6	NP_057349.2
ZNF12	NM_006956.3	c.550T>C	p.Cys184Arg	missense_variant	6/6		NP_008887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF12	ENST00000405858.6	c.664T>C	p.Cys222Arg	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1
ZNF12	ENST00000404360.5	c.442T>C	p.Cys148Arg	missense_variant	5/5	1		ENSP00000384405.1
ZNF12	ENST00000342651.9	c.550T>C	p.Cys184Arg	missense_variant	6/6	2		ENSP00000344745.5
ENSG00000228010	ENST00000366167.2	n.136-16023A>G		intron_variant		4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.664T>C (p.C222R) alteration is located in exon 5 (coding exon 4) of the ZNF12 gene. This alteration results from a T to C substitution at nucleotide position 664, causing the cysteine (C) at amino acid position 222 to be replaced by an arginine (R). 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	Benign	0.15
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	.;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.50	T;T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.0	.;M;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Pathogenic	-8.7	D;D;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.0050	D;D;D
Polyphen		0.93, 0.92	.;P;P
Vest4		0.56
MutPred		0.74		.;Gain of disorder (P = 0.04);.;
MVP		0.56
MPC		0.43
ClinPred		0.97	D
GERP RS		4.0
Varity_R		0.80
gMVP		0.31

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: chr7-6731909;