Genetic Variant ZNF77:p.Tyr492* (chr19-2933651-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021217.3(ZNF77):c.1476C>G(p.Tyr492*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000687 in 1,607,958 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0038 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00037 ( 6 hom. )

Consequence

ZNF77
NM_021217.3 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

ZNF77 (HGNC:13150): (zinc finger protein 77) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF77 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF77	NM_021217.3 link	c.1476C>G	p.Tyr492*	stop_gained	Exon 4 of 4	ENST00000314531.5	NP_067040.1	Q15935
ZNF77	NM_001426550.1 link	c.936C>G	p.Tyr312*	stop_gained	Exon 3 of 3		NP_001413479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF77	ENST00000314531.5 link	c.1476C>G	p.Tyr492*	stop_gained	Exon 4 of 4	1	NM_021217.3	ENSP00000319053.3		Q15935

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

568

AN:

151390

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000210

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00108

AC:

269

AN:

249570

Hom.:

AF XY:

0.000749

AC XY:

101

AN XY:

134922

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.000529

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:

0.0000177

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000366

AC:

533

AN:

1456452

Hom.:

Cov.:

AF XY:

0.000334

AC XY:

242

AN XY:

724348

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.000550

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.000947

GnomAD4 genome

AF:

0.00377

AC:

571

AN:

151506

Hom.:

Cov.:

AF XY:

0.00358

AC XY:

265

AN XY:

74058

show subpopulations

Gnomad4 AFR

AF:

0.0133

Gnomad4 AMR

AF:

0.000919

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.00433

ESP6500AA

AF:

0.0141

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00134

AC:

163

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 04, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Pathogenic

0.19

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.000090

Vest4

0.0090

GERP RS

-1.5

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