Variant 19-48286244-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153608.4(ZNF114):c.620T>C(p.Val207Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,614,140 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.027 ( 182 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 191 hom. )

Consequence

ZNF114
NM_153608.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0700

Variant links:

Genes affected

ZNF114 (HGNC:12894): (zinc finger protein 114) Enables identical protein binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ZNF114 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036190152).

BP6

Variant 19-48286244-T-C is Benign according to our data. Variant chr19-48286244-T-C is described in ClinVar as [Benign]. Clinvar id is 769027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF114	NM_153608.4 link	c.620T>C	p.Val207Ala	missense_variant	6/6	ENST00000595607.6	NP_705836.1	Q8NC26-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF114	ENST00000595607.6 link	c.620T>C	p.Val207Ala	missense_variant	6/6	1	NM_153608.4	ENSP00000469998.1	Q8NC26-1
ZNF114	ENST00000315849.5 link	c.620T>C	p.Val207Ala	missense_variant	5/5	2		ENSP00000318898.1	Q8NC26-1
ZNF114	ENST00000600687.5 link	c.620T>C	p.Val207Ala	missense_variant	5/5	5		ENSP00000471727.1	Q8NC26-1

Frequencies

GnomAD3 genomes

AF:

0.0274

AC:

4161

AN:

152136

Hom.:

180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0930

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00785

AC:

1974

AN:

251396

Hom.:

AF XY:

0.00588

AC XY:

799

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.0921

Gnomad AMR exome

AF:

0.00509

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000695

Gnomad OTH exome

AF:

0.00538

GnomAD4 exome

AF:

0.00353

AC:

5163

AN:

1461886

Hom.:

191

Cov.:

AF XY:

0.00315

AC XY:

2293

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0978

Gnomad4 AMR exome

AF:

0.00599

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000569

Gnomad4 OTH exome

AF:

0.00762

GnomAD4 genome

AF:

0.0274

AC:

4177

AN:

152254

Hom.:

182

Cov.:

AF XY:

0.0266

AC XY:

1979

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0931

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.00617

Hom.:

Bravo

AF:

0.0312

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0872

AC:

384

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00933

AC:

1133

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.4

DANN

Benign

0.78

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.31

.;.;T

MetaRNN

Benign

0.0036

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.28

.;.;N

REVEL

Benign

0.012

Sift

Benign

0.051

.;.;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.14

B;B;B

Vest4

0.039

MVP

0.072

MPC

0.33

ClinPred

0.0016

GERP RS

0.81

Varity_R

0.030

gMVP

0.019

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over