Variant 20-59191171-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178457.3(ZNF831):c.152C>G(p.Pro51Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,601,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. P51H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ZNF831
NM_178457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042644024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF831	NM_178457.3 linkuse as main transcript	c.152C>G	p.Pro51Arg	missense_variant	2/6	ENST00000371030.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF831	ENST00000371030.4 linkuse as main transcript	c.152C>G	p.Pro51Arg	missense_variant	2/6	1	NM_178457.3	P1
ZNF831	ENST00000637017.1 linkuse as main transcript	c.152C>G	p.Pro51Arg	missense_variant	4/8	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152220

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000343

AC:

AN:

233560

Hom.:

AF XY:

0.0000468

AC XY:

AN XY:

128290

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000281

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1449538

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

721222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000586

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000367

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000415

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2023

The c.152C>G (p.P51R) alteration is located in exon 1 (coding exon 1) of the ZNF831 gene. This alteration results from a C to G substitution at nucleotide position 152, causing the proline (P) at amino acid position 51 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0012

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.20

.;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.042

Sift

Uncertain

0.0080

.;D

Sift4G

Benign

0.23

.;T

Polyphen

1.0

D;D

Vest4

0.23

MutPred

0.25

Loss of catalytic residue at P50 (P = 0.0121);Loss of catalytic residue at P50 (P = 0.0121);

MVP

0.085

MPC

0.79

ClinPred

0.15

Varity_R

0.11

gMVP

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over