Variant 19-2850611-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000334241.9(ZNF555):c.28G>C(p.Ala10Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF555
ENST00000334241.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF555	NM_152791.5 linkuse as main transcript	c.28G>C	p.Ala10Pro	missense_variant	2/4	ENST00000334241.9	NP_690004.4
ZNF555	NM_001172775.2 linkuse as main transcript	c.28G>C	p.Ala10Pro	missense_variant	2/4		NP_001166246.1
ZNF555	XM_011527716.3 linkuse as main transcript	c.34G>C	p.Ala12Pro	missense_variant	2/4		XP_011526018.1
ZNF555	XM_017026375.2 linkuse as main transcript	c.34G>C	p.Ala12Pro	missense_variant	2/4		XP_016881864.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF555	ENST00000334241.9 linkuse as main transcript	c.28G>C	p.Ala10Pro	missense_variant	2/4	1	NM_152791.5	ENSP00000334853	P4	Q8NEP9-1
	ENST00000589365.1 linkuse as main transcript	n.398-3227C>G		intron_variant, non_coding_transcript_variant		4
ZNF555	ENST00000591539.1 linkuse as main transcript	c.28G>C	p.Ala10Pro	missense_variant	2/4	2		ENSP00000467893	A2	Q8NEP9-4
ZNF555	ENST00000585966.5 linkuse as main transcript	c.-69G>C		5_prime_UTR_variant	2/4	4		ENSP00000466982

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 15, 2023

The c.28G>C (p.A10P) alteration is located in exon 2 (coding exon 2) of the ZNF555 gene. This alteration results from a G to C substitution at nucleotide position 28, causing the alanine (A) at amino acid position 10 to be replaced by a proline (P). 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

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;.

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.23

T;T

M_CAP

Benign

0.0055

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.3

H;H

MutationTaster

Benign

0.86

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.7

D;.

REVEL

Benign

0.21

Sift

Uncertain

0.015

D;.

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.81

MutPred

0.68

Loss of stability (P = 0.0752);Loss of stability (P = 0.0752);

MVP

0.41

MPC

0.32

ClinPred

1.0

GERP RS

2.6

Varity_R

0.77

gMVP

0.60

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