Variant 19-2851555-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 ENST00000334241.9(ZNF555):c.218C>T(p.Thr73Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,612,800 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 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

ZNF555
ENST00000334241.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.964

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 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=0.058595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF555	NM_152791.5 linkuse as main transcript	c.218C>T	p.Thr73Met	missense_variant	3/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2 linkuse as main transcript	c.218C>T	p.Thr73Met	missense_variant	3/4		NP_001166246.1
ZNF555	XM_011527716.3 linkuse as main transcript	c.224C>T	p.Thr75Met	missense_variant	3/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.224C>T	p.Thr75Met	missense_variant	3/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9 linkuse as main transcript	c.218C>T	p.Thr73Met	missense_variant	3/4	1	NM_152791.5	ENSP00000334853	P4	Q8NEP9-1
	ENST00000589365.1 linkuse as main transcript	n.398-4171G>A		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1 linkuse as main transcript	c.218C>T	p.Thr73Met	missense_variant	3/4	2		ENSP00000467893	A2	Q8NEP9-4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.122C>T	p.Thr41Met	missense_variant	3/4	4		ENSP00000466982

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000959

AC:

AN:

250146

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135292

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000264

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:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000993

AC:

145

AN:

1460536

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

726634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000271

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000954

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000112

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000752

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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 16, 2024

The c.218C>T (p.T73M) alteration is located in exon 3 (coding exon 3) of the ZNF555 gene. This alteration results from a C to T substitution at nucleotide position 218, causing the threonine (T) at amino acid position 73 to be replaced by a methionine (M). 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

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.41

DEOGEN2

Benign

0.044

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.056

T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.63

N;.;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.24

N;.;.

REVEL

Benign

0.031

Sift

Benign

0.085

T;.;.

Sift4G

Benign

0.21

T;T;T

Polyphen

0.021

B;.;.

Vest4

0.12

MVP

0.085

MPC

0.047

ClinPred

0.039

GERP RS

0.25

Varity_R

0.014

gMVP

0.086

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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