dbSNP rs553602761: ZNF77:p.Arg508Cys (chr19-2933605-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021217.3(ZNF77):c.1522C>T(p.Arg508Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000319 in 1,596,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R508H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ZNF77
NM_021217.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.640

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12724116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021217.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF77	NM_021217.3	MANE Select	c.1522C>T	p.Arg508Cys	missense	Exon 4 of 4	NP_067040.1	Q15935
	ZNF77	NM_001426550.1		c.982C>T	p.Arg328Cys	missense	Exon 3 of 3	NP_001413479.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF77	ENST00000314531.5	TSL:1 MANE Select	c.1522C>T	p.Arg508Cys	missense	Exon 4 of 4	ENSP00000319053.3	Q15935
ZNF77	ENST00000915162.1		c.1519C>T	p.Arg507Cys	missense	Exon 4 of 4	ENSP00000585221.1
ZNF77	ENST00000863233.1		c.898C>T	p.Arg300Cys	missense	Exon 4 of 4	ENSP00000533292.1

Frequencies

GnomAD3 genomes

AF:

0.0000992

AC:

AN:

151260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000970

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000592

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000798

AC:

AN:

250768

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1445092

Hom.:

Cov.:

AF XY:

0.0000264

AC XY:

AN XY:

718484

show subpopulations

African (AFR)

AF:

0.000272

AC:

AN:

33094

American (AMR)

AF:

0.000254

AC:

AN:

43366

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25938

East Asian (EAS)

AF:

0.0000256

AC:

AN:

38992

South Asian (SAS)

AF:

0.00

AC:

AN:

83904

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53134

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1101212

Other (OTH)

AF:

0.0000335

AC:

AN:

59766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000991

AC:

AN:

151376

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

41360

American (AMR)

AF:

0.000395

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000195

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000592

AC:

AN:

67584

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000565

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000579

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.000070

LIST_S2

Benign

0.69

M_CAP

Benign

0.0032

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

0.64

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.039

Sift

Benign

0.050

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.21

MutPred

0.49

Loss of MoRF binding (P = 0.0133)

MVP

0.47

MPC

0.35

ClinPred

0.19

GERP RS

-1.8

Varity_R

0.10

gMVP

0.040

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over