Variant 19-40074892-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142578.2(ZNF780A):c.1550C>G(p.Ser517Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,612,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF780A
NM_001142578.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.43

Variant links:

Genes affected

ZNF780A (HGNC:27603): (zinc finger protein 780A) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF780A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102773964).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF780A	NM_001142578.2 linkuse as main transcript	c.1550C>G	p.Ser517Cys	missense_variant	6/6	ENST00000683561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF780A	ENST00000683561.1 linkuse as main transcript	c.1550C>G	p.Ser517Cys	missense_variant	6/6		NM_001142578.2	A2	O75290-1

Frequencies

GnomAD3 genomes

AF:

0.000173

AC:

AN:

150090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000589

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000662

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:

0.000489

GnomAD3 exomes

AF:

0.0000477

AC:

AN:

251368

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000173

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000180

AC:

AN:

150218

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

AN XY:

73464

show subpopulations

Gnomad4 AFR

AF:

0.000612

Gnomad4 AMR

AF:

0.0000661

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:

0.000483

Bravo

AF:

0.000151

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Sep 14, 2022

The c.1553C>G (p.S518C) alteration is located in exon 6 (coding exon 4) of the ZNF780A gene. This alteration results from a C to G substitution at nucleotide position 1553, causing the serine (S) at amino acid position 518 to be replaced by a cysteine (C). 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

0.090

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0092

M_CAP

Benign

0.0013

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.27

REVEL

Benign

0.037

Sift4G

Uncertain

0.013

D;D;D;D;D

Polyphen

0.97

.;D;.;D;.

Vest4

0.071

MutPred

0.41

.;Loss of ubiquitination at K521 (P = 0.0528);.;Loss of ubiquitination at K521 (P = 0.0528);.;

MVP

0.37

MPC

0.34

ClinPred

0.15

GERP RS

-2.2

Varity_R

0.099

gMVP

0.012

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