Variant chr7-149266390-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001195220.2(ZNF783):c.80A>G(p.Gln27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000743 in 1,599,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 0 hom. )

Consequence

ZNF783
NM_001195220.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.295

Variant links:

Genes affected

ZNF783 (HGNC:27222): (zinc finger protein 783) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF783 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=0.017780423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF783	NM_001195220.2 link	c.80A>G	p.Gln27Arg	missense_variant	2/6	ENST00000434415.6	NP_001182149.1	Q6ZMS7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF783	ENST00000434415.6 link	c.80A>G	p.Gln27Arg	missense_variant	2/6	5	NM_001195220.2	ENSP00000410890.1	Q6ZMS7-2
ZNF783	ENST00000378052.5 link	n.80A>G		non_coding_transcript_exon_variant	2/14	2		ENSP00000367291.1	Q6ZMS7-1
ZNF783	ENST00000476295.5 link	n.80A>G		non_coding_transcript_exon_variant	2/11	2		ENSP00000418666.1	Q6ZMS7-1

Frequencies

GnomAD3 genomes

AF:

0.000632

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.000749

AC:

178

AN:

237622

Hom.:

AF XY:

0.000780

AC XY:

101

AN XY:

129542

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000611

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.000671

GnomAD4 exome

AF:

0.000754

AC:

1091

AN:

1447580

Hom.:

Cov.:

AF XY:

0.000812

AC XY:

585

AN XY:

720500

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000605

Gnomad4 ASJ exome

AF:

0.000996

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000244

Gnomad4 FIN exome

AF:

0.000376

Gnomad4 NFE exome

AF:

0.000838

Gnomad4 OTH exome

AF:

0.000879

GnomAD4 genome

AF:

0.000645

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000623

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000750

AC:

EpiCase

AF:

0.00213

EpiControl

AF:

0.00178

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

Aug 10, 2021

The c.80A>G (p.Q27R) alteration is located in exon 2 (coding exon 2) of the ZNF783 gene. This alteration results from a A to G substitution at nucleotide position 80, causing the glutamine (Q) at amino acid position 27 to be replaced by an arginine (R). 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

0.075

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.9

DANN

Benign

0.86

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.15

M_CAP

Benign

0.0091

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

REVEL

Benign

0.027

Sift

Benign

0.033

Sift4G

Benign

0.54

Vest4

0.23

MVP

0.014

MPC

0.44

ClinPred

0.0080

GERP RS

2.3

gMVP

0.11

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