Variant 10-43609306-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145312.4(ZNF485):c.203A>G(p.Glu68Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZNF485
NM_145312.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.998

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18422738).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF485	NM_145312.4 linkuse as main transcript	c.203A>G	p.Glu68Gly	missense_variant	4/5	ENST00000361807.8	NP_660355.2	Q8NCK3-1A0A024R7T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF485	ENST00000361807.8 linkuse as main transcript	c.203A>G	p.Glu68Gly	missense_variant	4/5	1	NM_145312.4	ENSP00000354694.3	Q8NCK3-1
ZNF485	ENST00000374435.3 linkuse as main transcript	c.203A>G	p.Glu68Gly	missense_variant	4/5	1		ENSP00000363558.3	Q8NCK3-1
ZNF485	ENST00000430885.5 linkuse as main transcript	c.203A>G	p.Glu68Gly	missense_variant	4/5	2		ENSP00000393570.1	C9JV60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.203A>G (p.E68G) alteration is located in exon 4 (coding exon 3) of the ZNF485 gene. This alteration results from a A to G substitution at nucleotide position 203, causing the glutamic acid (E) at amino acid position 68 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

T;T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.34

.;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.;L

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.059

Sift

Benign

0.073

T;D;T

Sift4G

Benign

0.10

T;D;T

Polyphen

0.99

D;.;D

Vest4

0.18

MutPred

0.31

Loss of disorder (P = 0.0991);Loss of disorder (P = 0.0991);Loss of disorder (P = 0.0991);

MVP

0.46

MPC

0.53

ClinPred

0.74

GERP RS

1.7

Varity_R

0.12

gMVP

0.059

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over