19-19711870-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021030.3(ZNF14):​c.1411G>A​(p.Gly471Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,898 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: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.35
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22436813).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF14NM_021030.3 linkc.1411G>A p.Gly471Arg 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.1411G>A p.Gly471Arg missense_variant Exon 4 of 4 1 NM_021030.3 ENSP00000340514.2 P17017

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251260
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
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:
0.0000178
AC:
26
AN:
1461774
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000144
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74304
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000385
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 31, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1411G>A (p.G471R) 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 1411, causing the glycine (G) at amino acid position 471 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
Uncertain
0.37
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.0062
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.32
T
PROVEAN
Pathogenic
-7.4
D
REVEL
Benign
0.054
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.015
D
Polyphen
1.0
D
Vest4
0.17
MutPred
0.30
Gain of solvent accessibility (P = 0.0037);
MVP
0.58
MPC
0.42
ClinPred
0.84
D
GERP RS
0.54
Varity_R
0.43
gMVP
0.015

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: rs759564885; hg19: chr19-19822679; API