Genetic Variant ZNF180:p.Pro465Leu (chr19-44477006-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001278509.3(ZNF180):c.1394C>T(p.Pro465Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF180
NM_001278509.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

Publications

1 publications found

Variant links:

Genes affected

ZNF180 (HGNC:12970): (zinc finger protein 180) Zinc finger proteins have been shown to interact with nucleic acids and to have diverse functions. The zinc finger domain is a conserved amino acid sequence motif containing 2 specifically positioned cysteines and 2 histidines that are involved in coordinating zinc. Kruppel-related proteins form 1 family of zinc finger proteins. See MIM 604749 for additional information on zinc finger proteins.[supplied by OMIM, Jul 2002]

ZNF180 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278509.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF180	NM_001278509.3	MANE Select	c.1394C>T	p.Pro465Leu	missense	Exon 5 of 5	NP_001265438.2	Q9UJW8-2
ZNF180	NM_013256.7		c.1475C>T	p.Pro492Leu	missense	Exon 5 of 5	NP_037388.3	Q9UJW8-1
ZNF180	NM_001288759.4		c.1472C>T	p.Pro491Leu	missense	Exon 5 of 5	NP_001275688.2	Q9UJW8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF180	ENST00000592529.6	TSL:2 MANE Select	c.1394C>T	p.Pro465Leu	missense	Exon 5 of 5	ENSP00000468021.1	Q9UJW8-2
ZNF180	ENST00000221327.9	TSL:1	c.1475C>T	p.Pro492Leu	missense	Exon 5 of 5	ENSP00000221327.3
ZNF180	ENST00000590088.5	TSL:1	n.*1282C>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000468523.1	K7ES30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251374

AF XY:

0.0000147

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Benign

0.00010

LIST_S2

Benign

0.56

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.30

PhyloP100

4.3

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-9.7

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.43

MutPred

0.67

Loss of disorder (P = 0.0375)

MVP

0.69

MPC

0.33

ClinPred

1.0

GERP RS

4.1

gMVP

0.10

Mutation Taster

=88/12

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over