Genetic Variant ZNF727:p.Arg119Cys (chr7-64077404-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001159522.3(ZNF727):c.355C>T(p.Arg119Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000438 in 1,551,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ZNF727
NM_001159522.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.00

Publications

0 publications found

Variant links:

Genes affected

ZNF727 (HGNC:22785): (zinc finger protein 727) 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF727 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02461785).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001159522.3. 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
	ZNF727	NM_001159522.3	MANE Select	c.355C>T	p.Arg119Cys	missense	Exon 4 of 4	NP_001152994.1	A8MUV8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF727	ENST00000456806.3	TSL:4 MANE Select	c.355C>T	p.Arg119Cys	missense	Exon 4 of 4	ENSP00000485448.1	A8MUV8
ZNF727	ENST00000889951.1		c.331C>T	p.Arg111Cys	missense	Exon 4 of 4	ENSP00000560010.1
ZNF727	ENST00000889950.1		c.259C>T	p.Arg87Cys	missense	Exon 3 of 3	ENSP00000560009.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000190

AC:

AN:

158024

AF XY:

0.0000360

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000457

AC:

AN:

1399634

Hom.:

Cov.:

AF XY:

0.0000420

AC XY:

AN XY:

690300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31590

American (AMR)

AF:

0.000112

AC:

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35720

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.0000538

AC:

AN:

1079000

Other (OTH)

AF:

0.0000172

AC:

AN:

58106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

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:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41524

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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:

0.0000658

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000377

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

0.10

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.9

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00026

LIST_S2

Benign

0.039

M_CAP

Benign

0.0022

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.82

PhyloP100

-1.0

PrimateAI

Benign

0.24

Sift4G

Benign

0.10

Polyphen

0.13

Vest4

0.095

MVP

0.081

ClinPred

0.022

GERP RS

-1.1

Varity_R

0.13

gMVP

0.025

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