dbSNP rs375204197: ZNF880:p.Asn88Lys (chr19-52374423-C-A) – 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_001145434.2(ZNF880):c.264C>A(p.Asn88Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,278 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. Synonymous variant affecting the same amino acid position (i.e. N88N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF880
NM_001145434.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0950

Publications

0 publications found

Variant links:

Genes affected

ZNF880 (HGNC:37249): (zinc finger protein 880) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF880 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=0.07787019).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145434.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF880	NM_001145434.2	MANE Select	c.264C>A	p.Asn88Lys	missense	Exon 3 of 4	NP_001138906.1	Q6PDB4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF880	ENST00000422689.3	TSL:2 MANE Select	c.264C>A	p.Asn88Lys	missense	Exon 3 of 4	ENSP00000406318.2	Q6PDB4-1
ZNF880	ENST00000344085.9	TSL:1	c.235+29C>A		intron	N/A	ENSP00000343625.5	Q6PDB4-2
ZNF880	ENST00000906539.1		c.264C>A	p.Asn88Lys	missense	Exon 3 of 5	ENSP00000576598.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459278

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725616

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

85854

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110652

Other (OTH)

AF:

0.00

AC:

AN:

60336

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.24

(source)

DANN

Benign

0.13

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.17

M_CAP

Benign

0.0022

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.94

PhyloP100

-0.095

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.054

Sift

Benign

0.27

Sift4G

Benign

0.94

Polyphen

0.0

Vest4

0.16

MutPred

0.34

Gain of ubiquitination at N88 (P = 0.0069)

MVP

0.040

MPC

0.053

ClinPred

0.041

GERP RS

0.94

Varity_R

0.037

gMVP

0.020

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over