rs1780076589

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016265.4(ZNF12):​c.959C>T​(p.Thr320Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. T320K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF12
NM_016265.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.49
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27573705).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF12NM_016265.4 linkc.959C>T p.Thr320Ile missense_variant Exon 5 of 5 ENST00000405858.6 NP_057349.2 P17014-1
ZNF12NM_006956.3 linkc.845C>T p.Thr282Ile missense_variant Exon 6 of 6 NP_008887.2 P17014-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF12ENST00000405858.6 linkc.959C>T p.Thr320Ile missense_variant Exon 5 of 5 1 NM_016265.4 ENSP00000385939.1 P17014-1
ZNF12ENST00000404360.5 linkc.737C>T p.Thr246Ile missense_variant Exon 5 of 5 1 ENSP00000384405.1 P17014-4
ZNF12ENST00000342651.9 linkc.845C>T p.Thr282Ile missense_variant Exon 6 of 6 2 ENSP00000344745.5 P17014-5
ENSG00000228010ENST00000366167.2 linkn.136-16318G>A intron_variant Intron 2 of 3 4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461862
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727230
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
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
0.77
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T;.
Eigen
Benign
-0.026
Eigen_PC
Benign
-0.086
FATHMM_MKL
Benign
0.0038
N
LIST_S2
Benign
0.18
T;T;T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.28
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
.;M;.
PrimateAI
Uncertain
0.67
T
PROVEAN
Uncertain
-4.3
D;D;D
REVEL
Benign
0.076
Sift
Uncertain
0.0040
D;D;D
Sift4G
Uncertain
0.011
D;D;D
Polyphen
0.76, 0.93
.;P;P
Vest4
0.40
MutPred
0.44
.;Loss of disorder (P = 0.0367);.;
MVP
0.31
MPC
0.77
ClinPred
0.98
D
GERP RS
1.3
Varity_R
0.14
gMVP
0.079

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: chr7-6731614; API