Genetic Variant NM_021217.3:c.298C>T (chr19-2936537-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021217.3(ZNF77):c.298C>T(p.Gln100*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 1,601,876 control chromosomes in the GnomAD database, including 1,731 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.034 ( 118 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1613 hom. )

Consequence

ZNF77
NM_021217.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0480

Publications

27 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF77	NM_021217.3 link	c.298C>T	p.Gln100*	stop_gained	Exon 3 of 4	ENST00000314531.5	NP_067040.1	Q15935
ZNF77	NM_001426550.1 link	c.-243C>T		5_prime_UTR_variant	Exon 2 of 3		NP_001413479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF77	ENST00000314531.5 link	c.298C>T	p.Gln100*	stop_gained	Exon 3 of 4	1	NM_021217.3	ENSP00000319053.3		Q15935

Frequencies

GnomAD3 genomes

AF:

0.0339

AC:

5156

AN:

152170

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0205

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.0223

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0496

Gnomad OTH

AF:

0.0331

GnomAD2 exomes

AF:

0.0311

AC:

7408

AN:

238526

AF XY:

0.0319

show subpopulations

Gnomad AFR exome

AF:

0.0185

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0556

Gnomad EAS exome

AF:

0.000169

Gnomad FIN exome

AF:

0.0140

Gnomad NFE exome

AF:

0.0457

Gnomad OTH exome

AF:

0.0293

GnomAD4 exome

AF:

0.0446

AC:

64582

AN:

1449588

Hom.:

1613

Cov.:

AF XY:

0.0437

AC XY:

31547

AN XY:

721164

show subpopulations

African (AFR)

AF:

0.0198

AC:

640

AN:

32402

American (AMR)

AF:

0.0162

AC:

670

AN:

41260

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

1519

AN:

25840

East Asian (EAS)

AF:

0.000128

AC:

AN:

39214

South Asian (SAS)

AF:

0.0217

AC:

1811

AN:

83458

European-Finnish (FIN)

AF:

0.0149

AC:

796

AN:

53330

Middle Eastern (MID)

AF:

0.0232

AC:

133

AN:

5724

European-Non Finnish (NFE)

AF:

0.0512

AC:

56715

AN:

1108456

Other (OTH)

AF:

0.0383

AC:

2293

AN:

59904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2958

5916

8874

11832

14790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2102

4204

6306

8408

10510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0339

AC:

5160

AN:

152288

Hom.:

118

Cov.:

AF XY:

0.0319

AC XY:

2374

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0205

AC:

852

AN:

41558

American (AMR)

AF:

0.0223

AC:

341

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0553

AC:

192

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.0207

AC:

100

AN:

4832

European-Finnish (FIN)

AF:

0.0153

AC:

162

AN:

10620

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0496

AC:

3374

AN:

68012

Other (OTH)

AF:

0.0327

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

251

501

752

1002

1253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0433

Hom.:

591

Bravo

AF:

0.0330

TwinsUK

AF:

0.0526

AC:

195

ALSPAC

AF:

0.0464

AC:

179

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.0437

AC:

376

ExAC

AF:

0.0309

AC:

3752

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Benign

0.94

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.026

PhyloP100

0.048

Vest4

0.022

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=174/26

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over