Variant 19-57830533-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.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,549,478 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 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

ZNF587B
NM_001376223.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.909

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=0.039552093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF587B	NM_001376223.1 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/3	ENST00000594901.2	NP_001363152.1
ZNF587B	NM_001204818.2 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/4		NP_001191747.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ZNF587B	ENST00000594901.2 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/3	4	NM_001376223.1	ENSP00000469623	P4
ZNF587B	ENST00000442832.8 linkuse as main transcript	c.5C>T	p.Ala2Val	missense_variant	1/4	2		ENSP00000392410
ZNF587B	ENST00000594328.1 linkuse as main transcript	c.-114-8490C>T		intron_variant		2		ENSP00000472004
ZNF587B	ENST00000651253.2 linkuse as main transcript	c.34-8490C>T		intron_variant				ENSP00000499083	A2

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

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:

0.00191

GnomAD4 exome

AF:

0.00000930

AC:

AN:

1397204

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

689152

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000689

GnomAD4 genome

AF:

0.000118

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000915

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:

0.00189

Bravo

AF:

0.000280

ExAC

AF:

0.0000113

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

Jan 19, 2024

The c.5C>T (p.A2V) alteration is located in exon 1 (coding exon 1) of the ZNF587B gene. This alteration results from a C to T substitution at nucleotide position 5, causing the alanine (A) at amino acid position 2 to be replaced by a valine (V). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

9.3

DANN

Benign

0.97

DEOGEN2

Benign

0.0070

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.29

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.040

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.81

L;.

PROVEAN

Benign

0.020

N;.

REVEL

Benign

0.075

Sift

Benign

0.097

T;.

Sift4G

Benign

0.21

T;T

Polyphen

0.66

P;.

Vest4

0.092

MutPred

0.49

Loss of disorder (P = 0.0551);Loss of disorder (P = 0.0551);

MVP

0.030

MPC

0.55

ClinPred

0.13

GERP RS

-0.13

Varity_R

0.018

gMVP

0.27

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