Variant 19-36818923-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_206894.4(ZNF790):c.1421G>C(p.Gly474Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZNF790
NM_206894.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.840

Variant links:

Genes affected

ZNF790 (HGNC:33114): (zinc finger protein 790) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF790 links:

ZNF790-AS1 (HGNC:):

ZNF790-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29261255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF790	NM_206894.4 linkuse as main transcript	c.1421G>C	p.Gly474Ala	missense_variant	5/5	ENST00000356725.9	NP_996777.2	Q6PG37B4DMI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF790	ENST00000356725.9 linkuse as main transcript	c.1421G>C	p.Gly474Ala	missense_variant	5/5	2	NM_206894.4	ENSP00000349161.3		Q6PG37

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250406

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458404

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725480

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

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

Jul 14, 2023

The c.1421G>C (p.G474A) alteration is located in exon 5 (coding exon 4) of the ZNF790 gene. This alteration results from a G to C substitution at nucleotide position 1421, causing the glycine (G) at amino acid position 474 to be replaced by an alanine (A). 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

0.34

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

T;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.14

.;T;.;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.29

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

M;M;M;M

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-4.7

D;.;.;.

REVEL

Benign

0.082

Sift

Uncertain

0.021

D;.;.;.

Sift4G

Uncertain

0.010

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.20

MutPred

0.38

Loss of ubiquitination at K470 (P = 0.058);Loss of ubiquitination at K470 (P = 0.058);Loss of ubiquitination at K470 (P = 0.058);Loss of ubiquitination at K470 (P = 0.058);

MVP

0.68

MPC

0.29

ClinPred

0.97

GERP RS

3.1

Varity_R

0.46

gMVP

0.027

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