Variant chr19-57841229-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001376223.1(ZNF587B):c.555A>T(p.Leu185Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF587B
NM_001376223.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -2.29

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06754452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1 linkuse as main transcript	c.555A>T	p.Leu185Phe	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2 linkuse as main transcript	c.555A>T	p.Leu185Phe	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.555A>T	p.Leu185Phe	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623	P4
ZNF587B	ENST00000651253.2 linkuse as main transcript	c.552A>T	p.Leu184Phe	missense_variant	3/3			ENSP00000499083	A2
ZNF587B	ENST00000594328.1 linkuse as main transcript	c.405A>T	p.Leu135Phe	missense_variant	4/4	2		ENSP00000472004
ZNF587B	ENST00000442832.8 linkuse as main transcript	c.555A>T	p.Leu185Phe	missense_variant	3/4	2		ENSP00000392410

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727220

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.555A>T (p.L185F) alteration is located in exon 3 (coding exon 3) of the ZNF587B gene. This alteration results from a A to T substitution at nucleotide position 555, causing the leucine (L) at amino acid position 185 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.19

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00083

LIST_S2

Benign

0.35

T;T;T

M_CAP

Benign

0.00075

MetaRNN

Benign

0.068

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

.;L;.

PROVEAN

Benign

-0.020

.;N;.

REVEL

Benign

0.012

Sift

Benign

0.54

.;T;.

Sift4G

Benign

0.57

T;T;T

Polyphen

0.090

.;B;.

Vest4

0.026, 0.061

MutPred

0.40

.;Gain of catalytic residue at L185 (P = 0.199);Gain of catalytic residue at L185 (P = 0.199);

MVP

0.030

MPC

0.97

ClinPred

0.059

GERP RS

-4.3

Varity_R

0.021

gMVP

0.024

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