Variant 19-55642963-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000325333.10(ZNF580):c.455G>A(p.Cys152Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF580
ENST00000325333.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

Variant links:

Genes affected

ZNF580 (HGNC:29473): (zinc finger protein 580) Enables sequence-specific double-stranded DNA binding activity. Involved in several processes, including cellular response to hydrogen peroxide; positive regulation of cell migration; and positive regulation of interleukin-8 production. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF580 links:

ZNF581 (HGNC:25017): (zinc finger protein 581) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF581 links:

CCDC106 (HGNC:30181): (coiled-coil domain containing 106) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC106 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF580	NM_207115.2 linkuse as main transcript	c.455G>A	p.Cys152Tyr	missense_variant	2/2	ENST00000325333.10	NP_996998.1
ZNF580	NM_001163423.2 linkuse as main transcript	c.455G>A	p.Cys152Tyr	missense_variant	2/2		NP_001156895.1
ZNF580	NM_016202.2 linkuse as main transcript	c.455G>A	p.Cys152Tyr	missense_variant	1/1		NP_057286.1
ZNF581	XM_017026867.2 linkuse as main transcript	c.-19-1590G>A		intron_variant			XP_016882356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF580	ENST00000325333.10 linkuse as main transcript	c.455G>A	p.Cys152Tyr	missense_variant	2/2	1	NM_207115.2	ENSP00000320050	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1251022

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

609926

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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.:

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, 2023

The c.455G>A (p.C152Y) alteration is located in exon 1 (coding exon 1) of the ZNF580 gene. This alteration results from a G to A substitution at nucleotide position 455, causing the cysteine (C) at amino acid position 152 to be replaced by a tyrosine (Y). 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

1.0

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

T;T;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

.;.;D

M_CAP

Pathogenic

0.85

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

4.0

H;H;H

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Pathogenic

-11

D;D;D

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;D

Vest4

0.67

MutPred

0.76

Gain of glycosylation at P149 (P = 0.1131);Gain of glycosylation at P149 (P = 0.1131);Gain of glycosylation at P149 (P = 0.1131);

MVP

0.69

MPC

2.3

ClinPred

1.0

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.92

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over