Genetic Variant ZNF862:p.Pro105Pro (chr7-149847808-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001099220.3(ZNF862):c.315G>A(p.Pro105Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00803 in 1,613,788 control chromosomes in the GnomAD database, including 165 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 157 hom. )

Consequence

ZNF862
NM_001099220.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.48

Publications

1 publications found

Variant links:

Genes affected

ZNF862 (HGNC:34519): (zinc finger protein 862) Predicted to enable metal ion binding activity and protein dimerization 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]

ZNF862 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 7-149847808-G-A is Benign according to our data. Variant chr7-149847808-G-A is described in ClinVar as Benign. ClinVar VariationId is 781916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00577 (878/152234) while in subpopulation SAS AF = 0.0382 (184/4818). AF 95% confidence interval is 0.0337. There are 8 homozygotes in GnomAd4. There are 460 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099220.3. 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
	ZNF862	NM_001099220.3	MANE Select	c.315G>A	p.Pro105Pro	synonymous	Exon 4 of 8	NP_001092690.1	O60290-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF862	ENST00000223210.5	TSL:5 MANE Select	c.315G>A	p.Pro105Pro	synonymous	Exon 4 of 8	ENSP00000223210.4	O60290-1
	ZNF862	ENST00000460379.1	TSL:4	c.63G>A	p.Pro21Pro	synonymous	Exon 4 of 4	ENSP00000417450.1	C9JB70

Frequencies

GnomAD3 genomes

AF:

0.00579

AC:

880

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0386

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00734

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00912

AC:

2269

AN:

248784

AF XY:

0.0110

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00200

Gnomad NFE exome

AF:

0.00602

Gnomad OTH exome

AF:

0.00845

GnomAD4 exome

AF:

0.00827

AC:

12085

AN:

1461554

Hom.:

157

Cov.:

AF XY:

0.00926

AC XY:

6733

AN XY:

727040

show subpopulations

African (AFR)

AF:

0.000777

AC:

AN:

33478

American (AMR)

AF:

0.00300

AC:

134

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

299

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.0413

AC:

3560

AN:

86220

European-Finnish (FIN)

AF:

0.00249

AC:

133

AN:

53382

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00660

AC:

7335

AN:

1111800

Other (OTH)

AF:

0.00878

AC:

530

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

678

1356

2034

2712

3390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.00577

AC:

878

AN:

152234

Hom.:

Cov.:

AF XY:

0.00618

AC XY:

460

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41542

American (AMR)

AF:

0.00334

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.0382

AC:

184

AN:

4818

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00734

AC:

499

AN:

68010

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

147

196

245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00617

Hom.:

Bravo

AF:

0.00446

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00840

EpiControl

AF:

0.00652

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

(source)

DANN

Benign

0.37

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over