Genetic Variant NM_207115.2:c.436G>C (chr19-55642944-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207115.2(ZNF580):c.436G>C(p.Ala146Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,285,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A146T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

ZNF580
NM_207115.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.369

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.120037526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF580	NM_207115.2 link	c.436G>C	p.Ala146Pro	missense_variant	Exon 2 of 2	ENST00000325333.10	NP_996998.1	Q9UK33
ZNF580	NM_001163423.2 link	c.436G>C	p.Ala146Pro	missense_variant	Exon 2 of 2		NP_001156895.1	Q9UK33
ZNF580	NM_016202.2 link	c.436G>C	p.Ala146Pro	missense_variant	Exon 1 of 1		NP_057286.1	Q9UK33
ZNF581	XM_017026867.2 link	c.-19-1609G>C		intron_variant	Intron 1 of 1		XP_016882356.1	Q9P0T4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF580	ENST00000325333.10 link	c.436G>C	p.Ala146Pro	missense_variant	Exon 2 of 2	1	NM_207115.2	ENSP00000320050.4		Q9UK33

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.78e-7

AC:

AN:

1285558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

629744

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25766

American (AMR)

AF:

0.00

AC:

AN:

19934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19340

East Asian (EAS)

AF:

0.00

AC:

AN:

29474

South Asian (SAS)

AF:

0.00

AC:

AN:

63564

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

9.71e-7

AC:

AN:

1030226

Other (OTH)

AF:

0.00

AC:

AN:

52946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.32

.;.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.54

N;N;N

PhyloP100

0.37

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.073

Sift

Benign

0.24

T;T;T

Sift4G

Benign

0.16

T;T;T

Polyphen

0.97

D;D;D

Vest4

0.18

MutPred

0.36

Gain of glycosylation at A146 (P = 0.0279);Gain of glycosylation at A146 (P = 0.0279);Gain of glycosylation at A146 (P = 0.0279);

MVP

0.16

MPC

2.1

ClinPred

0.35

GERP RS

2.7

Varity_R

0.18

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over