Variant 19-2851585-T-C 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_152791.5(ZNF555):c.248T>C(p.Val83Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,611,270 control chromosomes in the GnomAD database, including 1 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 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000042 ( 1 hom. )

Consequence

ZNF555
NM_152791.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.130

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:

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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=0.03504932).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF555	NM_152791.5 linkuse as main transcript	c.248T>C	p.Val83Ala	missense_variant	3/4	ENST00000334241.9	NP_690004.4	Q8NEP9-1
ZNF555	NM_001172775.2 linkuse as main transcript	c.248T>C	p.Val83Ala	missense_variant	3/4		NP_001166246.1	Q8NEP9-4
ZNF555	XM_011527716.3 linkuse as main transcript	c.254T>C	p.Val85Ala	missense_variant	3/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.254T>C	p.Val85Ala	missense_variant	3/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF555	ENST00000334241.9 linkuse as main transcript	c.248T>C	p.Val83Ala	missense_variant	3/4	1	NM_152791.5	ENSP00000334853.3	Q8NEP9-1
ZNF555	ENST00000591539.1 linkuse as main transcript	c.248T>C	p.Val83Ala	missense_variant	3/4	2		ENSP00000467893.1	Q8NEP9-4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.152T>C	p.Val51Ala	missense_variant	3/4	4		ENSP00000466982.1	K7ENK0
ENSG00000267063	ENST00000589365.1 linkuse as main transcript	n.398-4201A>G		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000483

AC:

AN:

248316

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000891

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:

0.0000620

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1459152

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

725984

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000159

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.0000547

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

Mar 28, 2022

The c.248T>C (p.V83A) alteration is located in exon 3 (coding exon 3) of the ZNF555 gene. This alteration results from a T to C substitution at nucleotide position 248, causing the valine (V) at amino acid position 83 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.7

DANN

Benign

0.13

DEOGEN2

Benign

0.032

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.11

T;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.1

N;.;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

N;.;.

REVEL

Benign

0.032

Sift

Benign

0.70

T;.;.

Sift4G

Benign

0.81

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.087

MVP

0.076

MPC

0.047

ClinPred

0.020

GERP RS

1.5

Varity_R

0.073

gMVP

0.072

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