Genetic Variant ZNF831:p.Gln96Glu (chr20-59191305-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178457.3(ZNF831):c.286C>G(p.Gln96Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000486 in 1,440,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

ZNF831
NM_178457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14883152).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF831	NM_178457.3 link	c.286C>G	p.Gln96Glu	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.286C>G	p.Gln96Glu	missense_variant	Exon 2 of 6	1	NM_178457.3	ENSP00000360069.2		Q5JPB2
ZNF831	ENST00000637017.1 link	c.286C>G	p.Gln96Glu	missense_variant	Exon 4 of 8	5		ENSP00000490240.1		Q5JPB2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000470

AC:

AN:

212980

Hom.:

AF XY:

0.00000853

AC XY:

AN XY:

117184

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000645

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000486

AC:

AN:

1440410

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714994

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000775

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000838

AC:

Asia WGS

AF:

0.000289

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

Mar 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286C>G (p.Q96E) 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 286, causing the glutamine (Q) at amino acid position 96 to be replaced by a glutamic acid (E). 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

0.17

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0070

T;T

Eigen

Benign

0.0035

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

M;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

.;N

REVEL

Benign

0.033

Sift

Benign

0.047

.;D

Sift4G

Benign

0.25

.;T

Polyphen

0.70

P;P

Vest4

0.20

MutPred

0.16

Gain of glycosylation at P97 (P = 0.0727);Gain of glycosylation at P97 (P = 0.0727);

MVP

0.030

MPC

0.40

ClinPred

0.23

GERP RS

4.7

Varity_R

0.15

gMVP

0.30

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