Variant 19-57841126-G-A 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_001376223.1(ZNF587B):c.452G>A(p.Ser151Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF587B
NM_001376223.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.44

Variant links:

Genes affected

ZNF587B (HGNC:37142): (zinc finger protein 587B) 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]

ZNF587B 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=0.07035598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1 linkuse as main transcript	c.452G>A	p.Ser151Asn	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2 linkuse as main transcript	c.452G>A	p.Ser151Asn	missense_variant	3/4		NP_001191747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF587B	ENST00000594901.2 linkuse as main transcript	c.452G>A	p.Ser151Asn	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623	P4
ZNF587B	ENST00000651253.2 linkuse as main transcript	c.449G>A	p.Ser150Asn	missense_variant	3/3			ENSP00000499083	A2
ZNF587B	ENST00000594328.1 linkuse as main transcript	c.302G>A	p.Ser101Asn	missense_variant	4/4	2		ENSP00000472004
ZNF587B	ENST00000442832.8 linkuse as main transcript	c.452G>A	p.Ser151Asn	missense_variant	3/4	2		ENSP00000392410

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000294

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727236

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:

0.0000387

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 08, 2023

The c.452G>A (p.S151N) alteration is located in exon 3 (coding exon 3) of the ZNF587B gene. This alteration results from a G to A substitution at nucleotide position 452, causing the serine (S) at amino acid position 151 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.20

DANN

Benign

0.70

DEOGEN2

Benign

0.0061

T;T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.040

T;T;T

M_CAP

Benign

0.00078

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.56

.;N;.

PROVEAN

Benign

-0.47

.;N;.

REVEL

Benign

0.0050

Sift

Benign

0.38

.;T;.

Sift4G

Benign

0.67

T;T;T

Polyphen

0.15

.;B;.

Vest4

0.040, 0.060

MutPred

0.29

.;Loss of phosphorylation at S151 (P = 0.0262);Loss of phosphorylation at S151 (P = 0.0262);

MVP

0.040

MPC

0.32

ClinPred

0.039

GERP RS

-2.8

Varity_R

0.028

gMVP

0.0075

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