chr19-48285836-C-T

Variant summary

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

The NM_153608.4(ZNF114):​c.212C>T​(p.Ala71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

ZNF114
NM_153608.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.62
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]

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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=0.035013914).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF114NM_153608.4 linkc.212C>T p.Ala71Val missense_variant Exon 6 of 6 ENST00000595607.6 NP_705836.1 Q8NC26-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF114ENST00000595607.6 linkc.212C>T p.Ala71Val missense_variant Exon 6 of 6 1 NM_153608.4 ENSP00000469998.1 Q8NC26-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.212C>T (p.A71V) 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 212, causing the alanine (A) at amino acid position 71 to be replaced by a valine (V). 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
0.26
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
1.1
DANN
Benign
0.17
DEOGEN2
Benign
0.011
T;T;T;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0029
N
LIST_S2
Benign
0.49
.;.;T;T
M_CAP
Benign
0.00084
T
MetaRNN
Benign
0.035
T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-1.3
N;N;.;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.13
.;.;.;N
REVEL
Benign
0.0050
Sift
Benign
1.0
.;.;.;T
Sift4G
Benign
0.76
T;T;T;T
Polyphen
0.11
B;B;.;B
Vest4
0.041
MutPred
0.22
Loss of disorder (P = 0.1004);Loss of disorder (P = 0.1004);.;Loss of disorder (P = 0.1004);
MVP
0.16
MPC
0.45
ClinPred
0.041
T
GERP RS
0.92
Varity_R
0.021
gMVP
0.058

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48789093; API