Genetic Variant ZNF181:p.Val102Glu (chr19-34740686-T-A) – 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_001029997.4(ZNF181):c.305T>A(p.Val102Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000422 in 1,611,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF181
NM_001029997.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.42

Variant links:

Genes affected

ZNF181 (HGNC:12971): (zinc finger protein 181) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2003]

ZNF181 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=0.029396296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF181	NM_001029997.4 link	c.305T>A	p.Val102Glu	missense_variant	Exon 4 of 4	ENST00000492450.3	NP_001025168.2	Q2M3W8-1B4DM69

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF181	ENST00000492450.3 link	c.305T>A	p.Val102Glu	missense_variant	Exon 4 of 4	1	NM_001029997.4	ENSP00000420727.1		Q2M3W8-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000870

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000562

AC:

AN:

248922

Hom.:

AF XY:

0.0000518

AC XY:

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.000772

Gnomad AMR exome

AF:

0.0000583

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1459922

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.000840

Gnomad4 AMR exome

AF:

0.0000450

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000243

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.000870

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 04, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.305T>A (p.V102E) alteration is located in exon 4 (coding exon 4) of the ZNF181 gene. This alteration results from a T to A substitution at nucleotide position 305, causing the valine (V) at amino acid position 102 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.011

.;T;.;.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.54

T;T;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.029

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.68

.;.;.;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

0.43

N;.;.;N;N

REVEL

Benign

0.056

Sift

Benign

0.24

T;.;.;T;T

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.012

.;.;.;.;B

Vest4

0.22

MVP

0.21

MPC

1.1

ClinPred

0.036

GERP RS

2.1

Varity_R

0.074

gMVP

0.17

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