Variant 19-57840858-G-T 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.184G>T(p.Asp62Tyr) 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. 11/19 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: 0.0000058 ( 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: -0.955

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:

ENSG00000268750 (HGNC:):

ENSG00000268750 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=0.09051934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1 linkuse as main transcript	c.184G>T	p.Asp62Tyr	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2 linkuse as main transcript	c.184G>T	p.Asp62Tyr	missense_variant	3/4		NP_001191747.1	E7ETH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF587B	ENST00000594901.2 linkuse as main transcript	c.184G>T	p.Asp62Tyr	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623.1	M0QY62
ZNF587B	ENST00000442832.8 linkuse as main transcript	c.184G>T	p.Asp62Tyr	missense_variant	3/4	2		ENSP00000392410.2	E7ETH6
ENSG00000268750	ENST00000593873.6 linkuse as main transcript	c.34-17718G>T		intron_variant		4		ENSP00000469133.2	M0QXF5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000576

AC:

AN:

1389306

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

684872

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:

0.00000741

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

Mar 11, 2024

The c.184G>T (p.D62Y) alteration is located in exon 3 (coding exon 3) of the ZNF587B gene. This alteration results from a G to T substitution at nucleotide position 184, causing the aspartic acid (D) at amino acid position 62 to be replaced by a tyrosine (Y). 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

0.21

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.092

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.091

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.0

.;M;.

PROVEAN

Pathogenic

-5.8

.;D;.

REVEL

Benign

0.024

Sift

Uncertain

0.0020

.;D;.

Sift4G

Uncertain

0.043

D;T;D

Polyphen

0.88

.;P;.

Vest4

0.25, 0.31

MutPred

0.32

.;Gain of phosphorylation at D62 (P = 0.0662);Gain of phosphorylation at D62 (P = 0.0662);

MVP

0.048

MPC

0.70

ClinPred

0.41

GERP RS

-2.5

Varity_R

0.055

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over