19-2852451-A-G

Position:

chr19-2852451-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152791.5(ZNF555):c.386A>G(p.His129Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000207 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

ZNF555
NM_152791.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0700

Variant links:

Genes affected

ZNF555 (HGNC:28382): (zinc finger protein 555) 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]

ZNF555 links:

ENSG00000267063 (HGNC:):

ENSG00000267063 links:

Genome browser will be placed here

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=0.09540668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5 linkuse as main transcript	c.386A>G	p.His129Arg	missense_variant	4/4	ENST00000334241.9	NP_690004.4	Q8NEP9-1
ZNF555	NM_001172775.2 linkuse as main transcript	c.383A>G	p.His128Arg	missense_variant	4/4		NP_001166246.1	Q8NEP9-4
ZNF555	XM_011527716.3 linkuse as main transcript	c.392A>G	p.His131Arg	missense_variant	4/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.389A>G	p.His130Arg	missense_variant	4/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF555	ENST00000334241.9 linkuse as main transcript	c.386A>G	p.His129Arg	missense_variant	4/4	1	NM_152791.5	ENSP00000334853.3	Q8NEP9-1
ZNF555	ENST00000591539.1 linkuse as main transcript	c.383A>G	p.His128Arg	missense_variant	4/4	2		ENSP00000467893.1	Q8NEP9-4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.290A>G	p.His97Arg	missense_variant	4/4	4		ENSP00000466982.1	K7ENK0
ENSG00000267063	ENST00000589365.1 linkuse as main transcript	n.398-5067T>C		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251406

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000211

AC:

308

AN:

1461862

Hom.:

Cov.:

AF XY:

0.000213

AC XY:

155

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000171

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.0000962

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:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000229

Hom.:

Bravo

AF:

0.000140

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Aug 02, 2021

The c.386A>G (p.H129R) alteration is located in exon 4 (coding exon 4) of the ZNF555 gene. This alteration results from a A to G substitution at nucleotide position 386, causing the histidine (H) at amino acid position 129 to be replaced by an arginine (R). 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

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.74

CADD

Benign

9.3

DANN

Benign

0.76

DEOGEN2

Benign

0.22

T;.;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.010

T;T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.095

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.95

L;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

N;.;.

REVEL

Benign

0.080

Sift

Benign

0.071

T;.;.

Sift4G

Benign

0.097

T;D;T

Polyphen

0.0020

B;.;.

Vest4

0.042

MVP

0.14

MPC

0.048

ClinPred

0.027

GERP RS

3.6

Varity_R

0.071

gMVP

0.12

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