Variant 19-44476733-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001278509.3(ZNF180):c.1667G>A(p.Gly556Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,002 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 1 hom. )

Consequence

ZNF180
NM_001278509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF180	NM_001278509.3 link	c.1667G>A	p.Gly556Glu	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.1667G>A	p.Gly556Glu	missense_variant	5/5	2	NM_001278509.3	ENSP00000468021.1		A0A0A0MP75

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727226

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Dec 06, 2021

The c.1748G>A (p.G583E) alteration is located in exon 5 (coding exon 5) of the ZNF180 gene. This alteration results from a G to A substitution at nucleotide position 1748, causing the glycine (G) at amino acid position 583 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

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

.;T;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.000060

LIST_S2

Benign

0.33

.;T;T

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.53

D;D;D

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.4

D;D;.

REVEL

Benign

0.28

Sift

Pathogenic

0.0

D;D;.

Sift4G

Uncertain

0.023

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.55

MutPred

0.58

Gain of disorder (P = 0.0801);.;.;

MVP

0.46

MPC

0.36

ClinPred

1.0

GERP RS

5.7

gMVP

0.076

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