7-6691034-A-C

Position:

• chr7-6691034-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016265.4(ZNF12):​c.1908T>G​(p.Asn636Lys) 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. 14/21 in silico tools predict a benign 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: -6.33

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09624243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF12	NM_016265.4	c.1908T>G	p.Asn636Lys	missense_variant	5/5	ENST00000405858.6	NP_057349.2
ZNF12	NM_006956.3	c.1794T>G	p.Asn598Lys	missense_variant	6/6		NP_008887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF12	ENST00000405858.6	c.1908T>G	p.Asn636Lys	missense_variant	5/5	1	NM_016265.4	ENSP00000385939.1
ZNF12	ENST00000404360.5	c.1686T>G	p.Asn562Lys	missense_variant	5/5	1		ENSP00000384405.1
ZNF12	ENST00000342651.9	c.1794T>G	p.Asn598Lys	missense_variant	6/6	2		ENSP00000344745.5
ENSG00000228010	ENST00000366167.2	n.136-17267A>C		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

Aug 15, 2023

The c.1908T>G (p.N636K) alteration is located in exon 5 (coding exon 4) of the ZNF12 gene. This alteration results from a T to G substitution at nucleotide position 1908, causing the asparagine (N) at amino acid position 636 to be replaced by a lysine (K). 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	0.17
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.010
DANN	Benign	0.89
DEOGEN2	Benign	0.069	.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.025	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.096	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.11	.;N;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.054
Sift	Benign	0.099	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.68, 0.11	.;P;B
Vest4		0.36
MutPred		0.34		.;Gain of methylation at N636 (P = 0.0012);.;
MVP		0.13
MPC		0.55
ClinPred		0.55	D
GERP RS		-7.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.046

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: chr7-6730665;