19-19711785-C-T

Variant summary

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

The NM_021030.3(ZNF14):​c.1496G>A​(p.Gly499Glu) 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 1,461,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.570
Variant links:
Genes affected
ZNF14 (HGNC:12924): (zinc finger protein 14) The protein encoded by this gene contains a zinc finger and a Kruppel-associated box (KRAB) domain. KRAB domain is known to be involved in the transcriptional repression of a number of zinc finger proteins. [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=0.30269966).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF14NM_021030.3 linkc.1496G>A p.Gly499Glu missense_variant Exon 4 of 4 ENST00000344099.4 NP_066358.2 P17017

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF14ENST00000344099.4 linkc.1496G>A p.Gly499Glu missense_variant Exon 4 of 4 1 NM_021030.3 ENSP00000340514.2 P17017

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251254
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135788
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461394
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726994
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1496G>A (p.G499E) alteration is located in exon 4 (coding exon 4) of the ZNF14 gene. This alteration results from a G to A substitution at nucleotide position 1496, causing the glycine (G) at amino acid position 499 to be replaced by a glutamic acid (E). 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
Pathogenic
0.75
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.00079
N
LIST_S2
Benign
0.10
T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.30
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
2.0
M
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-6.5
D
REVEL
Benign
0.064
Sift
Benign
0.050
D
Sift4G
Uncertain
0.029
D
Polyphen
1.0
D
Vest4
0.19
MutPred
0.32
Gain of solvent accessibility (P = 0.024);
MVP
0.61
MPC
0.42
ClinPred
0.98
D
GERP RS
1.8
Varity_R
0.30
gMVP
0.010

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1252271697; hg19: chr19-19822594; API