19-19712313-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021030.3(ZNF14):​c.968G>A​(p.Arg323Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,613,674 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 2 hom. )

Consequence

ZNF14
NM_021030.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.19
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 Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.02008769).
BP6
Variant 19-19712313-C-T is Benign according to our data. Variant chr19-19712313-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3194043.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF14NM_021030.3 linkc.968G>A p.Arg323Gln 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.968G>A p.Arg323Gln missense_variant Exon 4 of 4 1 NM_021030.3 ENSP00000340514.2 P17017

Frequencies

GnomAD3 genomes
AF:
0.000283
AC:
43
AN:
151944
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000559
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000335
AC:
84
AN:
250650
Hom.:
0
AF XY:
0.000362
AC XY:
49
AN XY:
135536
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000636
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000755
AC:
1103
AN:
1461730
Hom.:
2
Cov.:
32
AF XY:
0.000711
AC XY:
517
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000937
Gnomad4 NFE exome
AF:
0.000915
Gnomad4 OTH exome
AF:
0.00106
GnomAD4 genome
AF:
0.000283
AC:
43
AN:
151944
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000559
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000579
Hom.:
0
Bravo
AF:
0.000332
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000264
AC:
32
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000872
EpiControl
AF:
0.000356

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 01, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.67
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
4.9
DANN
Benign
0.74
DEOGEN2
Benign
0.024
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.000040
N
LIST_S2
Benign
0.018
T
M_CAP
Benign
0.0014
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
1.5
L
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.72
N
REVEL
Benign
0.025
Sift
Benign
1.0
T
Sift4G
Benign
0.55
T
Polyphen
0.38
B
Vest4
0.032
MVP
0.21
MPC
0.41
ClinPred
0.033
T
GERP RS
-3.6
Varity_R
0.020
gMVP
0.0094

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: rs147048566; hg19: chr19-19823122; COSMIC: COSV105905387; COSMIC: COSV105905387; API