chr19-48285836-C-T

Variant names:

• chr19-48285836-C-T
• NM_153608.4:c.212C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.62

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]

ACMG classification

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
ZNF114	NM_153608.4	c.212C>T	p.Ala71Val	missense_variant	Exon 6 of 6	ENST00000595607.6	NP_705836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF114	ENST00000595607.6	c.212C>T	p.Ala71Val	missense_variant	Exon 6 of 6	1	NM_153608.4	ENSP00000469998.1

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

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;