Variant 19-57473600-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001144068.2(ZNF772):c.1021G>A(p.Glu341Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,613,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00084 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

ZNF772
NM_001144068.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03127113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF772	NM_001144068.2 linkuse as main transcript	c.1021G>A	p.Glu341Lys	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.1021G>A	p.Glu341Lys	missense_variant	4/4	2	NM_001144068.2	ENSP00000348992.3		Q68DY9-3
ENSG00000268163	ENST00000596831.1 linkuse as main transcript	c.199+2060G>A		intron_variant		2		ENSP00000470969.1		M0R036

Frequencies

GnomAD3 genomes

AF:

0.000842

AC:

128

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000912

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000680

AC:

171

AN:

251460

Hom.:

AF XY:

0.000773

AC XY:

105

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.00113

AC:

1650

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

813

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.000729

GnomAD4 genome

AF:

0.000842

AC:

128

AN:

152108

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000912

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000861

Hom.:

Bravo

AF:

0.000997

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000659

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00154

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

Jul 14, 2021

The c.1144G>A (p.E382K) alteration is located in exon 5 (coding exon 5) of the ZNF772 gene. This alteration results from a G to A substitution at nucleotide position 1144, causing the glutamic acid (E) at amino acid position 382 to be replaced by a lysine (K). 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

0.26

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

T;.;.;.;.

Eigen

Benign

0.069

Eigen_PC

Benign

0.0058

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.25

T;T;T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.031

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.035

N;.;.;.;.

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.6

D;D;D;.;.

REVEL

Benign

0.16

Sift

Benign

0.098

T;T;T;.;.

Sift4G

Uncertain

0.015

D;D;D;D;D

Polyphen

1.0

D;D;.;.;.

Vest4

0.26

MVP

0.45

MPC

0.86

ClinPred

0.054

GERP RS

4.1

Varity_R

0.32

gMVP

0.18

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