rs200296539

Variant names:

• chr7-6691414-T-A
• NM_016265.4:c.1528A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-6691414-T-A
• chr7-6691414-T-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.1528A>T​(p.Ile510Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I510V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF12 NM_016265.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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=0.1669924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF12	NM_016265.4	c.1528A>T	p.Ile510Phe	missense_variant	Exon 5 of 5	ENST00000405858.6	NP_057349.2
ZNF12	NM_006956.3	c.1414A>T	p.Ile472Phe	missense_variant	Exon 6 of 6		NP_008887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF12	ENST00000405858.6	c.1528A>T	p.Ile510Phe	missense_variant	Exon 5 of 5	1	NM_016265.4	ENSP00000385939.1
ZNF12	ENST00000404360.5	c.1306A>T	p.Ile436Phe	missense_variant	Exon 5 of 5	1		ENSP00000384405.1
ZNF12	ENST00000342651.9	c.1414A>T	p.Ile472Phe	missense_variant	Exon 6 of 6	2		ENSP00000344745.5
ENSG00000228010	ENST00000366167.2	n.136-16887T>A		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461716 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.86
DEOGEN2	Benign	0.056	.;T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.00042	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	.;L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.041
Sift	Benign	0.049	D;D;D
Sift4G	Uncertain	0.056	T;T;T
Polyphen		0.41, 0.22	.;B;B
Vest4		0.23
MutPred		0.28		.;Loss of phosphorylation at Y507 (P = 0.1205);.;
MVP		0.24
MPC		0.78
ClinPred		0.23	T
GERP RS		-1.1
Varity_R		0.079
gMVP		0.084

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: chr7-6731045;