Genetic Variant ZNF485:p.Pro10Leu (chr10-43608618-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_145312.4(ZNF485):c.29C>T(p.Pro10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,612,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ZNF485
NM_145312.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.600

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01270777).

BP6

Variant 10-43608618-C-T is Benign according to our data. Variant chr10-43608618-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3196096.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF485	NM_145312.4 link	c.29C>T	p.Pro10Leu	missense_variant	Exon 3 of 5	ENST00000361807.8	NP_660355.2	Q8NCK3-1A0A024R7T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF485	ENST00000361807.8 link	c.29C>T	p.Pro10Leu	missense_variant	Exon 3 of 5	1	NM_145312.4	ENSP00000354694.3	Q8NCK3-1
ZNF485	ENST00000374435.3 link	c.29C>T	p.Pro10Leu	missense_variant	Exon 3 of 5	1		ENSP00000363558.3	Q8NCK3-1
ZNF485	ENST00000430885.5 link	c.29C>T	p.Pro10Leu	missense_variant	Exon 3 of 5	2		ENSP00000393570.1	C9JV60

Frequencies

GnomAD3 genomes

AF:

0.0000855

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000185

AC:

AN:

249142

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

134592

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00139

Gnomad NFE exome

AF:

0.0000800

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.000140

AC:

204

AN:

1460850

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.000122

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000848

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000988

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 09, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.97

DANN

Benign

0.89

DEOGEN2

Benign

0.0055

T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.14

.;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-1.0

N;.;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.053

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.81

T;T;T

Polyphen

0.47

P;.;P

Vest4

0.074

MVP

0.21

MPC

0.12

ClinPred

0.0091

GERP RS

-0.35

Varity_R

0.037

gMVP

0.044

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