Genetic Variant ZNF114:p.Arg231Cys (chr19-48286315-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_153608.4(ZNF114):c.691C>T(p.Arg231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZNF114
NM_153608.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.28

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 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=0.06017846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF114	NM_153608.4 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 6 of 6	ENST00000595607.6	NP_705836.1	Q8NC26-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF114	ENST00000595607.6 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 6 of 6	1	NM_153608.4	ENSP00000469998.1	Q8NC26-1
ZNF114	ENST00000315849.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 5 of 5	2		ENSP00000318898.1	Q8NC26-1
ZNF114	ENST00000600687.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 5 of 5	5		ENSP00000471727.1	Q8NC26-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251284

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000555

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.691C>T (p.R231C) alteration is located in exon 5 (coding exon 3) of the ZNF114 gene. This alteration results from a C to T substitution at nucleotide position 691, causing the arginine (R) at amino acid position 231 to be replaced by a cysteine (C). 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

0.60

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.80

DEOGEN2

Benign

0.039

T;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.44

.;.;T

M_CAP

Benign

0.00059

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.3

.;.;N

REVEL

Benign

0.015

Sift

Benign

0.034

.;.;D

Sift4G

Uncertain

0.058

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.12

MutPred

0.43

Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);Loss of MoRF binding (P = 0.0094);

MVP

0.15

MPC

0.29

ClinPred

0.040

GERP RS

-3.6

Varity_R

0.041

gMVP

0.062

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