Variant chr19-44477123-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001278509.3(ZNF180):c.1277T>C(p.Ile426Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000896 in 1,613,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00094 ( 2 hom. )

Consequence

ZNF180
NM_001278509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.193

Variant links:

Genes affected

ZNF180 (HGNC:12970): (zinc finger protein 180) 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 2002]

ZNF180 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.042088956).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF180	NM_001278509.3 link	c.1277T>C	p.Ile426Thr	missense_variant	5/5	ENST00000592529.6	NP_001265438.2	Q9UJW8A0A0A0MP75

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF180	ENST00000592529.6 link	c.1277T>C	p.Ile426Thr	missense_variant	5/5	2	NM_001278509.3	ENSP00000468021.1		A0A0A0MP75

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000897

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000354

AC:

AN:

251166

Hom.:

AF XY:

0.000324

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.00

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:

0.000748

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000943

AC:

1378

AN:

1460850

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

646

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00138

GnomAD4 genome

AF:

0.000440

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000747

Hom.:

Bravo

AF:

0.000502

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000593

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

Apr 17, 2024

The c.1358T>C (p.I453T) alteration is located in exon 5 (coding exon 5) of the ZNF180 gene. This alteration results from a T to C substitution at nucleotide position 1358, causing the isoleucine (I) at amino acid position 453 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

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.0095

.;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.0

LIST_S2

Benign

0.38

.;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.042

T;T;T

MetaSVM

Benign

-0.92

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.8

N;N;.

REVEL

Benign

0.17

Sift

Benign

0.29

T;T;.

Sift4G

Benign

0.54

T;T;T

Polyphen

0.12

.;B;.

Vest4

0.17

MVP

0.55

MPC

0.076

ClinPred

0.034

GERP RS

4.1

gMVP

0.050

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