dbSNP rs114604989: ZNF831:p.Gly538Asp (chr20-59192632-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_178457.3(ZNF831):c.1613G>A(p.Gly538Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000831 in 1,498,698 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

ZNF831
NM_178457.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37

Publications

1 publications found

Variant links:

Genes affected

ZNF831 (HGNC:16167): (zinc finger protein 831) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ZNF831 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042366683).

BP6

Variant 20-59192632-G-A is Benign according to our data. Variant chr20-59192632-G-A is described in ClinVar as [Benign]. Clinvar id is 717048.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000415 (559/1346462) while in subpopulation AFR AF = 0.0171 (512/29926). AF 95% confidence interval is 0.0159. There are 4 homozygotes in GnomAdExome4. There are 256 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF831	NM_178457.3 link	c.1613G>A	p.Gly538Asp	missense_variant	Exon 2 of 6	ENST00000371030.4	NP_848552.1	Q5JPB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF831	ENST00000371030.4 link	c.1613G>A	p.Gly538Asp	missense_variant	Exon 2 of 6	1	NM_178457.3	ENSP00000360069.2		Q5JPB2
ZNF831	ENST00000637017.1 link	c.1613G>A	p.Gly538Asp	missense_variant	Exon 4 of 8	5		ENSP00000490240.1		Q5JPB2

Frequencies

GnomAD3 genomes

AF:

0.00450

AC:

684

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00135

AC:

160

AN:

118124

AF XY:

0.00112

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.000236

Gnomad ASJ exome

AF:

0.000348

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000188

Gnomad OTH exome

AF:

0.00129

GnomAD4 exome

AF:

0.000415

AC:

559

AN:

1346462

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

256

AN XY:

658682

show subpopulations

African (AFR)

AF:

0.0171

AC:

512

AN:

29926

American (AMR)

AF:

0.000481

AC:

AN:

27004

Ashkenazi Jewish (ASJ)

AF:

0.0000499

AC:

AN:

20028

East Asian (EAS)

AF:

0.00

AC:

AN:

36978

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5330

European-Non Finnish (NFE)

AF:

0.00000378

AC:

AN:

1058688

Other (OTH)

AF:

0.000504

AC:

AN:

55570

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00451

AC:

687

AN:

152236

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

328

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0160

AC:

663

AN:

41544

American (AMR)

AF:

0.00111

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00543

ESP6500AA

AF:

0.00990

AC:

ESP6500EA

AF:

0.000285

AC:

ExAC

AF:

0.00104

AC:

118

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.64

CADD

Benign

8.3

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.0048

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.58

.;T

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

N;N

PhyloP100

1.4

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.5

.;N

REVEL

Benign

0.030

Sift

Benign

0.094

.;T

Sift4G

Benign

0.11

.;T

Polyphen

0.023

B;B

Vest4

0.12

MVP

0.076

MPC

0.29

ClinPred

0.0026

GERP RS

3.3

Varity_R

0.045

gMVP

0.32

Mutation Taster

=96/4

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

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rs114604989

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over