Variant 19-57840970-C-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.296C>T(p.Pro99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,592,830 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 0.000026 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

ZNF587B
NM_001376223.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

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=0.048697263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1 linkuse as main transcript	c.296C>T	p.Pro99Leu	missense_variant	3/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2 linkuse as main transcript	c.296C>T	p.Pro99Leu	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.296C>T	p.Pro99Leu	missense_variant	3/3	4	NM_001376223.1	ENSP00000469623	P4
ZNF587B	ENST00000651253.2 linkuse as main transcript	c.293C>T	p.Pro98Leu	missense_variant	3/3			ENSP00000499083	A2
ZNF587B	ENST00000594328.1 linkuse as main transcript	c.146C>T	p.Pro49Leu	missense_variant	4/4	2		ENSP00000472004
ZNF587B	ENST00000442832.8 linkuse as main transcript	c.296C>T	p.Pro99Leu	missense_variant	3/4	2		ENSP00000392410

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

151068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000980

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000106

AC:

AN:

189394

Hom.:

AF XY:

0.00000984

AC XY:

AN XY:

101626

show subpopulations

Gnomad AFR exome

AF:

0.0000992

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000415

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000902

AC:

AN:

1441646

Hom.:

Cov.:

AF XY:

0.00000560

AC XY:

AN XY:

714732

show subpopulations

Gnomad4 AFR exome

AF:

0.0000303

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000636

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151184

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73860

show subpopulations

Gnomad4 AFR

AF:

0.0000977

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000841

AC:

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 08, 2022

The c.296C>T (p.P99L) alteration is located in exon 3 (coding exon 3) of the ZNF587B gene. This alteration results from a C to T substitution at nucleotide position 296, causing the proline (P) at amino acid position 99 to be replaced by a leucine (L). 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

0.18

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.59

DANN

Benign

0.19

DEOGEN2

Benign

0.061

T;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.067

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.049

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.11

.;N;.

PROVEAN

Uncertain

-2.5

.;D;.

REVEL

Benign

0.0070

Sift

Benign

1.0

.;T;.

Sift4G

Benign

0.88

T;T;T

Polyphen

0.037

.;B;.

Vest4

0.087, 0.11

MutPred

0.47

.;Gain of catalytic residue at P99 (P = 0.0503);Gain of catalytic residue at P99 (P = 0.0503);

MVP

0.067

MPC

0.33

ClinPred

0.030

GERP RS

-0.80

Varity_R

0.032

gMVP

0.021

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