Variant 19-57474027-C-G 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_001144068.2(ZNF772):c.594G>C(p.Glu198Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,022 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 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

ZNF772
NM_001144068.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.31

Variant links:

Genes affected

ZNF772 (HGNC:33106): (zinc finger protein 772) 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]

ZNF772 links:

ENSG00000268163 (HGNC:):

ENSG00000268163 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=0.06981099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF772	NM_001144068.2 linkuse as main transcript	c.594G>C	p.Glu198Asp	missense_variant	4/4	ENST00000356584.8	NP_001137540.1	Q68DY9-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF772	ENST00000356584.8 linkuse as main transcript	c.594G>C	p.Glu198Asp	missense_variant	4/4	2	NM_001144068.2	ENSP00000348992.3		Q68DY9-3
ENSG00000268163	ENST00000596831.1 linkuse as main transcript	c.199+1633G>C		intron_variant		2		ENSP00000470969.1		M0R036

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251404

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.000369

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461810

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000138

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000482

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000200

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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

Mar 30, 2024

The c.717G>C (p.E239D) alteration is located in exon 5 (coding exon 5) of the ZNF772 gene. This alteration results from a G to C substitution at nucleotide position 717, causing the glutamic acid (E) at amino acid position 239 to be replaced by an aspartic acid (D). 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

0.11

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.024

T;.;.;.;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.0091

T;T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.070

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

L;.;.;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.9

N;N;N;.;.

REVEL

Benign

0.025

Sift

Uncertain

0.0010

D;D;D;.;.

Sift4G

Benign

0.064

T;D;D;D;D

Polyphen

0.084

B;B;.;.;.

Vest4

0.050

MutPred

0.22

Loss of disorder (P = 0.179);.;.;.;.;

MVP

0.49

MPC

0.20

ClinPred

0.086

GERP RS

1.9

Varity_R

0.13

gMVP

0.082

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