19-55642707-G-A

Position:

chr19-55642707-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_207115.2(ZNF580):c.199G>A(p.Val67Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,495,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

ZNF580
NM_207115.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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 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=0.04387191).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF580	NM_207115.2 linkuse as main transcript	c.199G>A	p.Val67Met	missense_variant	2/2	ENST00000325333.10	NP_996998.1	Q9UK33
ZNF580	NM_001163423.2 linkuse as main transcript	c.199G>A	p.Val67Met	missense_variant	2/2		NP_001156895.1	Q9UK33
ZNF580	NM_016202.2 linkuse as main transcript	c.199G>A	p.Val67Met	missense_variant	1/1		NP_057286.1	Q9UK33
ZNF581	XM_017026867.2 linkuse as main transcript	c.-19-1846G>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.199G>A	p.Val67Met	missense_variant	2/2	1	NM_207115.2	ENSP00000320050.4		Q9UK33

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152128

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000390

AC:

AN:

102598

Hom.:

AF XY:

0.0000173

AC XY:

AN XY:

57802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000104

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000109

AC:

147

AN:

1343496

Hom.:

Cov.:

AF XY:

0.0000954

AC XY:

AN XY:

660198

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:

0.000135

Gnomad4 OTH exome

AF:

0.0000903

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74440

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:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000129

AC:

ExAC

AF:

0.0000364

AC:

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

Nov 27, 2023

The c.199G>A (p.V67M) 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 199, causing the valine (V) at amino acid position 67 to be replaced by a methionine (M). 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

0.59

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.70

T;.;.;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.044

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

.;N;N;.;N

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-0.92

.;N;N;.;N

REVEL

Benign

0.047

Sift

Benign

0.066

.;T;T;.;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.024

.;B;B;.;B

Vest4

0.24, 0.25, 0.24

MVP

0.043

MPC

1.6

ClinPred

0.15

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.079

gMVP

0.21

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