Genetic Variant NM_145312.4:c.442C>T (chr10-43616485-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_145312.4(ZNF485):c.442C>T(p.His148Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Consequence

ZNF485
NM_145312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

Publications

0 publications found

Variant links:

Genes affected

ZNF485 (HGNC:23440): (zinc finger protein 485) Predicted to enable DNA-binding transcription activator 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]

ZNF485 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145312.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF485	NM_145312.4	MANE Select	c.442C>T	p.His148Tyr	missense	Exon 5 of 5	NP_660355.2	Q8NCK3-1
ZNF485	NM_001318140.2		c.442C>T	p.His148Tyr	missense	Exon 5 of 5	NP_001305069.1	Q8NCK3-1
ZNF485	NM_001318141.2		c.442C>T	p.His148Tyr	missense	Exon 5 of 5	NP_001305070.1	Q8NCK3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF485	ENST00000361807.8	TSL:1 MANE Select	c.442C>T	p.His148Tyr	missense	Exon 5 of 5	ENSP00000354694.3	Q8NCK3-1
ZNF485	ENST00000374435.3	TSL:1	c.442C>T	p.His148Tyr	missense	Exon 5 of 5	ENSP00000363558.3	Q8NCK3-1
ZNF485	ENST00000896014.1		c.442C>T	p.His148Tyr	missense	Exon 4 of 4	ENSP00000566073.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2088

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

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

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

0.64

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.12

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.77

MetaSVM

Uncertain

0.78

MutationAssessor

Pathogenic

3.3

PhyloP100

4.9

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.7

REVEL

Pathogenic

0.70

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.34

MutPred

0.70

Gain of phosphorylation at H148 (P = 0.0744)

MVP

0.99

MPC

0.62

ClinPred

0.99

GERP RS

2.4

Varity_R

0.57

gMVP

0.14

Mutation Taster

=69/31

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over