Variant 19-48286558-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000595607.6(ZNF114):c.934G>A(p.Ala312Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,820 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: 0.0000055 ( 0 hom. )

Consequence

ZNF114
ENST00000595607.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500

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:

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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=0.08662933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF114	NM_153608.4 linkuse as main transcript	c.934G>A	p.Ala312Thr	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 linkuse as main transcript	c.934G>A	p.Ala312Thr	missense_variant	6/6	1	NM_153608.4	ENSP00000469998.1	Q8NC26-1
ZNF114	ENST00000315849.5 linkuse as main transcript	c.934G>A	p.Ala312Thr	missense_variant	5/5	2		ENSP00000318898.1	Q8NC26-1
ZNF114	ENST00000600687.5 linkuse as main transcript	c.934G>A	p.Ala312Thr	missense_variant	5/5	5		ENSP00000471727.1	Q8NC26-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.934G>A (p.A312T) alteration is located in exon 5 (coding exon 3) of the ZNF114 gene. This alteration results from a G to A substitution at nucleotide position 934, causing the alanine (A) at amino acid position 312 to be replaced by a threonine (T). 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

0.43

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.7

DANN

Benign

0.92

DEOGEN2

Benign

0.040

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.74

.;.;T

M_CAP

Benign

0.00070

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.50

N;N;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.0

.;.;N

REVEL

Benign

0.056

Sift

Benign

0.17

.;.;T

Sift4G

Uncertain

0.016

D;D;D

Polyphen

0.14

B;B;B

Vest4

0.041

MutPred

0.56

Gain of disorder (P = 0.0902);Gain of disorder (P = 0.0902);Gain of disorder (P = 0.0902);

MVP

0.11

MPC

0.44

ClinPred

0.099

GERP RS

-3.1

Varity_R

0.041

gMVP

0.014

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