Genetic Variant ZNF607:p.Lys531Arg (chr19-37698539-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032689.5(ZNF607):c.1592A>G(p.Lys531Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 1,613,740 control chromosomes in the GnomAD database, including 499,672 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.71 ( 39491 hom., cov: 31)

Exomes 𝑓: 0.79 ( 460181 hom. )

Consequence

ZNF607
NM_032689.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

39 publications found

Variant links:

Genes affected

ZNF607 (HGNC:28192): (zinc finger protein 607) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF607 links:

ENSG00000267552 (HGNC:):

ENSG00000267552 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.8106626E-7).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF607	NM_032689.5 link	c.1592A>G	p.Lys531Arg	missense_variant	Exon 5 of 5	ENST00000355202.9	NP_116078.4	Q96SK3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF607	ENST00000355202.9 link	c.1592A>G	p.Lys531Arg	missense_variant	Exon 5 of 5	2	NM_032689.5	ENSP00000347338.2		Q96SK3-1
ENSG00000267552	ENST00000586606.6 link	n.346+1246A>G		intron_variant	Intron 5 of 6	3		ENSP00000467889.1		K7EQM0

Frequencies

GnomAD3 genomes

AF:

0.708

AC:

107520

AN:

151794

Hom.:

39453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.564

Gnomad AMI

AF:

0.778

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.762

Gnomad EAS

AF:

0.310

Gnomad SAS

AF:

0.652

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.822

Gnomad OTH

AF:

0.716

GnomAD2 exomes

AF:

0.714

AC:

179413

AN:

251388

AF XY:

0.724

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.619

Gnomad ASJ exome

AF:

0.785

Gnomad EAS exome

AF:

0.303

Gnomad FIN exome

AF:

0.784

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.769

GnomAD4 exome

AF:

0.786

AC:

1149145

AN:

1461826

Hom.:

460181

Cov.:

AF XY:

0.785

AC XY:

571077

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.549

AC:

18388

AN:

33480

American (AMR)

AF:

0.628

AC:

28069

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

20471

AN:

26136

East Asian (EAS)

AF:

0.296

AC:

11735

AN:

39698

South Asian (SAS)

AF:

0.687

AC:

59276

AN:

86252

European-Finnish (FIN)

AF:

0.786

AC:

41984

AN:

53400

Middle Eastern (MID)

AF:

0.780

AC:

4501

AN:

5768

European-Non Finnish (NFE)

AF:

0.826

AC:

918124

AN:

1111972

Other (OTH)

AF:

0.772

AC:

46597

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14634

29268

43903

58537

73171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20760

41520

62280

83040

103800

<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:

0.708

AC:

107607

AN:

151914

Hom.:

39491

Cov.:

AF XY:

0.704

AC XY:

52256

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.564

AC:

23338

AN:

41400

American (AMR)

AF:

0.676

AC:

10303

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.762

AC:

2645

AN:

3472

East Asian (EAS)

AF:

0.310

AC:

1599

AN:

5150

South Asian (SAS)

AF:

0.654

AC:

3148

AN:

4812

European-Finnish (FIN)

AF:

0.779

AC:

8225

AN:

10554

Middle Eastern (MID)

AF:

0.820

AC:

241

AN:

294

European-Non Finnish (NFE)

AF:

0.822

AC:

55883

AN:

67958

Other (OTH)

AF:

0.718

AC:

1517

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1469

2937

4406

5874

7343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.774

Hom.:

156975

Bravo

AF:

0.694

TwinsUK

AF:

0.807

AC:

2991

ALSPAC

AF:

0.819

AC:

3155

ESP6500AA

AF:

0.570

AC:

2512

ESP6500EA

AF:

0.814

AC:

7002

ExAC

AF:

0.715

AC:

86783

Asia WGS

AF:

0.533

AC:

1853

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

7.8e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.88

L;.

PhyloP100

0.14

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.064

Sift

Benign

0.13

T;T

Sift4G

Uncertain

0.012

D;D

Polyphen

0.94

P;.

Vest4

0.023

MPC

0.28

ClinPred

0.021

GERP RS

1.2

Varity_R

0.12

gMVP

0.0040

Mutation Taster

=100/0

polymorphism (auto)

(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

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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