19-2852510-G-A

Position:

chr19-2852510-G-A

Variant summary

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

The NM_152791.5(ZNF555):c.445G>A(p.Gly149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ZNF555
NM_152791.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

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=0.13645953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5 linkuse as main transcript	c.445G>A	p.Gly149Arg	missense_variant	4/4	ENST00000334241.9	NP_690004.4	Q8NEP9-1
ZNF555	NM_001172775.2 linkuse as main transcript	c.442G>A	p.Gly148Arg	missense_variant	4/4		NP_001166246.1	Q8NEP9-4
ZNF555	XM_011527716.3 linkuse as main transcript	c.451G>A	p.Gly151Arg	missense_variant	4/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.448G>A	p.Gly150Arg	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.445G>A	p.Gly149Arg	missense_variant	4/4	1	NM_152791.5	ENSP00000334853.3	Q8NEP9-1
ZNF555	ENST00000591539.1 linkuse as main transcript	c.442G>A	p.Gly148Arg	missense_variant	4/4	2		ENSP00000467893.1	Q8NEP9-4
ENSG00000267063	ENST00000589365.1 linkuse as main transcript	n.398-5126C>T		intron_variant		4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.*14G>A		downstream_gene_variant		4		ENSP00000466982.1	K7ENK0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

251064

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461794

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 20, 2021

The c.445G>A (p.G149R) alteration is located in exon 4 (coding exon 4) of the ZNF555 gene. This alteration results from a G to A substitution at nucleotide position 445, causing the glycine (G) at amino acid position 149 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

0.13

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.26

T;.

Eigen

Benign

-0.90

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00067

LIST_S2

Benign

0.023

T;T

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-6.3

D;.

REVEL

Benign

0.19

Sift

Benign

0.040

D;.

Sift4G

Uncertain

0.038

D;D

Polyphen

0.96

D;.

Vest4

0.092

MutPred

0.63

Gain of MoRF binding (P = 0.0118);.;

MVP

0.66

MPC

0.047

ClinPred

0.50

GERP RS

-3.0

Varity_R

0.18

gMVP

0.090

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