Variant 19-2873551-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024967.3(ZNF556):c.59T>C(p.Leu20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF556
NM_024967.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00200

Variant links:

Genes affected

ZNF556 (HGNC:25669): (zinc finger protein 556) 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]

ZNF556 links:

ZNF556 (HGNC:):

ZNF556 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37200272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF556	NM_024967.3 linkuse as main transcript	c.59T>C	p.Leu20Ser	missense_variant	2/4	ENST00000307635.3	NP_079243.1
ZNF556	NM_001300843.2 linkuse as main transcript	c.59T>C	p.Leu20Ser	missense_variant	2/4		NP_001287772.1
ZNF556	NR_145838.2 linkuse as main transcript	n.146T>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF556	ENST00000307635.3 linkuse as main transcript	c.59T>C	p.Leu20Ser	missense_variant	2/4	2	NM_024967.3	ENSP00000302603.2	Q9HAH1
ZNF556	ENST00000586426.5 linkuse as main transcript	c.59T>C	p.Leu20Ser	missense_variant	2/4	1		ENSP00000467366.1	A0A0C4DGQ3
ZNF556	ENST00000586470.5 linkuse as main transcript	n.59T>C		non_coding_transcript_exon_variant	2/4	3		ENSP00000465533.1	K7EKA5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

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

Jun 06, 2023

The c.59T>C (p.L20S) alteration is located in exon 2 (coding exon 2) of the ZNF556 gene. This alteration results from a T to C substitution at nucleotide position 59, causing the leucine (L) at amino acid position 20 to be replaced by a serine (S). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.069

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.5

.;D

REVEL

Benign

0.042

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.33

MutPred

0.56

Loss of stability (P = 0.0198);Loss of stability (P = 0.0198);

MVP

0.18

MPC

0.34

ClinPred

0.85

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

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