19-19711656-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021030.3(ZNF14):​c.1625G>A​(p.Arg542His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.942
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017226964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF14NM_021030.3 linkc.1625G>A p.Arg542His 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.1625G>A p.Arg542His missense_variant Exon 4 of 4 1 NM_021030.3 ENSP00000340514.2 P17017

Frequencies

GnomAD3 genomes
AF:
0.0000396
AC:
6
AN:
151648
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:
0.00117
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:
0.0000916
AC:
23
AN:
251218
Hom.:
0
AF XY:
0.0000958
AC XY:
13
AN XY:
135766
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461854
Hom.:
0
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000453
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
151768
Hom.:
0
Cov.:
33
AF XY:
0.0000539
AC XY:
4
AN XY:
74200
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00117
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000988
AC:
12

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1625G>A (p.R542H) 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 1625, causing the arginine (R) at amino acid position 542 to be replaced by a histidine (H). 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
0.25
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
12
DANN
Benign
0.94
DEOGEN2
Benign
0.022
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.00012
N
LIST_S2
Benign
0.21
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.017
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.78
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.037
Sift
Benign
0.55
T
Sift4G
Benign
0.63
T
Polyphen
0.021
B
Vest4
0.079
MVP
0.21
MPC
0.26
ClinPred
0.095
T
GERP RS
-0.92
Varity_R
0.018
gMVP
0.026

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: rs138870060; hg19: chr19-19822465; API