Variant 19-2852414-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000334241.9(ZNF555):c.349A>G(p.Asn117Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000898 in 1,614,214 control chromosomes in the GnomAD database, including 4 homozygotes. 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 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00094 ( 3 hom. )

Consequence

ZNF555
ENST00000334241.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0170

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015057862).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF555	NM_152791.5 linkuse as main transcript	c.349A>G	p.Asn117Asp	missense_variant	4/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2 linkuse as main transcript	c.346A>G	p.Asn116Asp	missense_variant	4/4		NP_001166246.1
ZNF555	XM_011527716.3 linkuse as main transcript	c.355A>G	p.Asn119Asp	missense_variant	4/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.352A>G	p.Asn118Asp	missense_variant	4/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9 linkuse as main transcript	c.349A>G	p.Asn117Asp	missense_variant	4/4	1	NM_152791.5	ENSP00000334853	P4	Q8NEP9-1
	ENST00000589365.1 linkuse as main transcript	n.398-5030T>C		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1 linkuse as main transcript	c.346A>G	p.Asn116Asp	missense_variant	4/4	2		ENSP00000467893	A2	Q8NEP9-4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.253A>G	p.Asn85Asp	missense_variant	4/4	4		ENSP00000466982

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000553

AC:

139

AN:

251376

Hom.:

AF XY:

0.000707

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000748

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000936

AC:

1369

AN:

1461868

Hom.:

Cov.:

AF XY:

0.000963

AC XY:

700

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.000745

GnomAD4 genome

AF:

0.000525

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000859

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000889

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

Sep 27, 2021

The c.349A>G (p.N117D) 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 349, causing the asparagine (N) at amino acid position 117 to be replaced by an aspartic acid (D). 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

0.065

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.4

DANN

Benign

0.55

DEOGEN2

Benign

0.034

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00051

LIST_S2

Benign

0.025

T;T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.49

N;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;.;.

REVEL

Benign

0.0070

Sift

Benign

0.27

T;.;.

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.19

MVP

0.14

MPC

0.049

ClinPred

0.012

GERP RS

-0.86

Varity_R

0.076

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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