19-2933651-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_021217.3(ZNF77):c.1476C>G(p.Tyr492Ter) 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.17

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM4: Stoplost variant in NM_021217.3 Downstream stopcodon found after 7 codons.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF77	NM_021217.3	c.1476C>G	p.Tyr492Ter	stop_gained	4/4	ENST00000314531.5
ZNF77	XM_047439170.1	c.1380C>G	p.Tyr460Ter	stop_gained	4/4
ZNF77	XM_017027081.2	c.936C>G	p.Tyr312Ter	stop_gained	3/3
ZNF77	XM_047439171.1	c.936C>G	p.Tyr312Ter	stop_gained	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF77	ENST00000314531.5	c.1476C>G	p.Tyr492Ter	stop_gained	4/4	1	NM_021217.3	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 568 AN: 151390 Hom.: 2 Cov.: 33

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.: 2 AF XY: 0.000749 AC XY: 101 AN XY: 134922

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.: 6 Cov.: 78 AF XY: 0.000334 AC XY: 242 AN XY: 724348

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.: 2 Cov.: 33 AF XY: 0.00358 AC XY: 265 AN XY: 74058

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.: 0

Bravo AF: 0.00433

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.00 AC: 0

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 04, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Pathogenic	0.19
Cadd	Uncertain	25
Dann	Uncertain	0.98
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.000090	N
MutationTaster	Benign	1.0	D
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

Other links and lift over

dbSNP: rs34789013; hg19: chr19-2933649;