chr19-55642789-G-A

Position:

chr19-55642789-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_207115.2(ZNF580):c.281G>A(p.Cys94Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000025 in 1,558,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ZNF580
NM_207115.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF580	NM_207115.2 linkuse as main transcript	c.281G>A	p.Cys94Tyr	missense_variant	2/2	ENST00000325333.10	NP_996998.1	Q9UK33
ZNF580	NM_001163423.2 linkuse as main transcript	c.281G>A	p.Cys94Tyr	missense_variant	2/2		NP_001156895.1	Q9UK33
ZNF580	NM_016202.2 linkuse as main transcript	c.281G>A	p.Cys94Tyr	missense_variant	1/1		NP_057286.1	Q9UK33
ZNF581	XM_017026867.2 linkuse as main transcript	c.-19-1764G>A		intron_variant			XP_016882356.1	Q9P0T4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF580	ENST00000325333.10 linkuse as main transcript	c.281G>A	p.Cys94Tyr	missense_variant	2/2	1	NM_207115.2	ENSP00000320050.4		Q9UK33

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152244

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000263

AC:

AN:

1406234

Hom.:

Cov.:

AF XY:

0.0000215

AC XY:

AN XY:

696816

show subpopulations

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:

0.0000339

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000586

Hom.:

Bravo

AF:

0.0000113

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

Aug 10, 2024

The c.281G>A (p.C94Y) 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 281, causing the cysteine (C) at amino acid position 94 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

0.99

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T;.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.63

T;.;.;T;T

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.76

D;D;D;D;D

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.1

.;M;M;.;M

PrimateAI

Pathogenic

0.97

PROVEAN

Pathogenic

-10

.;D;D;.;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

.;D;D;.;D

Sift4G

Benign

0.077

T;D;D;T;D

Polyphen

0.84

.;P;P;.;P

Vest4

0.79, 0.76, 0.79

MutPred

0.44

Gain of phosphorylation at C94 (P = 0.0465);Gain of phosphorylation at C94 (P = 0.0465);Gain of phosphorylation at C94 (P = 0.0465);Gain of phosphorylation at C94 (P = 0.0465);Gain of phosphorylation at C94 (P = 0.0465);

MVP

0.59

MPC

1.5

ClinPred

1.0

GERP RS

3.0

Varity_R

0.88

gMVP

0.83

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

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