Variant 19-36748063-C-T 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_001193552.2(ZNF850):c.2977G>A(p.Gly993Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000235 in 1,560,444 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 0 hom. )

Consequence

ZNF850
NM_001193552.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.43

Variant links:

Genes affected

ZNF850 (HGNC:27994): (zinc finger protein 850) Predicted to enable DNA-binding transcription activator 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]

ZNF850 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=0.021768957).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF850	NM_001193552.2 linkuse as main transcript	c.2977G>A	p.Gly993Ser	missense_variant	5/5	ENST00000591344.2	NP_001180481.1
ZNF850	NM_001267779.2 linkuse as main transcript	c.2881G>A	p.Gly961Ser	missense_variant	4/4		NP_001254708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF850	ENST00000591344.2 linkuse as main transcript	c.2977G>A	p.Gly993Ser	missense_variant	5/5	1	NM_001193552.2	ENSP00000464976	P1
ZNF850	ENST00000614887.4 linkuse as main transcript	c.2881G>A	p.Gly961Ser	missense_variant	4/4	1		ENSP00000483509
ZNF850	ENST00000589390.5 linkuse as main transcript	c.235+13580G>A		intron_variant		3		ENSP00000465189

Frequencies

GnomAD3 genomes

AF:

0.0000748

AC:

AN:

147128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000632

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000196

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000126

AC:

AN:

175262

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

94154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000190

Gnomad ASJ exome

AF:

0.000113

Gnomad EAS exome

AF:

0.000314

Gnomad SAS exome

AF:

0.0000413

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000252

AC:

356

AN:

1413198

Hom.:

Cov.:

AF XY:

0.000247

AC XY:

173

AN XY:

699578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000133

Gnomad4 ASJ exome

AF:

0.0000393

Gnomad4 EAS exome

AF:

0.000188

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.0000224

Gnomad4 NFE exome

AF:

0.000301

Gnomad4 OTH exome

AF:

0.000170

GnomAD4 genome

AF:

0.0000747

AC:

AN:

147246

Hom.:

Cov.:

AF XY:

0.0000696

AC XY:

AN XY:

71828

show subpopulations

Gnomad4 AFR

AF:

0.0000251

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000633

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000196

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000793

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000503

AC:

Asia WGS

AF:

0.000289

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

Nov 17, 2022

The c.2977G>A (p.G993S) alteration is located in exon 5 (coding exon 4) of the ZNF850 gene. This alteration results from a G to A substitution at nucleotide position 2977, causing the glycine (G) at amino acid position 993 to be replaced by a serine (S). 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

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.023

DANN

Benign

0.81

DEOGEN2

Benign

0.0017

.;T

FATHMM_MKL

Benign

0.000010

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.022

T;T

MutationAssessor

Benign

-1.2

.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

Sift4G

Benign

1.0

T;T

Polyphen

0.12

.;B

Vest4

0.087

MVP

0.17

MPC

0.32

GERP RS

-4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.023

gMVP

0.035

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