Variant 19-9758603-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001077624.3(ZNF846):c.474T>G(p.Ser158Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,968 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF846
NM_001077624.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.310

Variant links:

Genes affected

ZNF846 (HGNC:27260): (zinc finger protein 846) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF846 links:

ZNF846 (HGNC:):

ZNF846 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=0.075660855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF846	NM_001077624.3 linkuse as main transcript	c.474T>G	p.Ser158Arg	missense_variant	6/6	ENST00000397902.7	NP_001071092.1	Q147U1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF846	ENST00000397902.7 linkuse as main transcript	c.474T>G	p.Ser158Arg	missense_variant	6/6	1	NM_001077624.3	ENSP00000380999.1		Q147U1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249108

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.00000342

AC:

AN:

1460968

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726686

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 29, 2021

The c.474T>G (p.S158R) alteration is located in exon 6 (coding exon 5) of the ZNF846 gene. This alteration results from a T to G substitution at nucleotide position 474, causing the serine (S) at amino acid position 158 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

0.17

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.70

CADD

Benign

6.6

DANN

Benign

0.87

DEOGEN2

Benign

0.0054

.;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.15

.;T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.076

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.48

.;.;N;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

.;.;N;.

REVEL

Benign

0.016

Sift

Benign

0.44

.;.;T;.

Sift4G

Benign

0.23

T;T;T;.

Polyphen

0.054

.;.;B;.

Vest4

0.14

MutPred

0.27

.;.;Gain of MoRF binding (P = 0.0241);.;

MVP

0.061

MPC

0.012

ClinPred

0.021

GERP RS

2.1

Varity_R

0.072

gMVP

0.029

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