Variant chr19-9610386-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000302851.8(ZNF561):c.1275A>G(p.Ile425Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,688 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF561
ENST00000302851.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.65

Variant links:

Genes affected

ZNF561 (HGNC:28684): (zinc finger protein 561) 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]

ZNF561 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=0.086915076).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF561	NM_152289.3 linkuse as main transcript	c.1275A>G	p.Ile425Met	missense_variant	6/6	ENST00000302851.8	NP_689502.2	Q8N587-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF561	ENST00000302851.8 linkuse as main transcript	c.1275A>G	p.Ile425Met	missense_variant	6/6	1	NM_152289.3	ENSP00000303915.3	Q8N587-1
ZNF561	ENST00000424629.5 linkuse as main transcript	c.1068A>G	p.Ile356Met	missense_variant	5/5	2		ENSP00000393074.1	A8KAD9
ZNF561	ENST00000326044 linkuse as main transcript	c.*919A>G		3_prime_UTR_variant	5/5	2		ENSP00000370284.2	F8W7U5
ZNF561	ENST00000444802.5 linkuse as main transcript	n.*330+3635A>G		intron_variant		5		ENSP00000402974.1	F2Z3H5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727116

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:

0.00000270

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

Mar 01, 2023

The c.1275A>G (p.I425M) alteration is located in exon 6 (coding exon 5) of the ZNF561 gene. This alteration results from a A to G substitution at nucleotide position 1275, causing the isoleucine (I) at amino acid position 425 to be replaced by a methionine (M). 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

0.19

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.7

DANN

Benign

0.89

DEOGEN2

Benign

0.0086

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.000030

LIST_S2

Benign

0.39

T;T

M_CAP

Benign

0.0021

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

.;M

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.42

N;N

REVEL

Benign

0.040

Sift

Benign

0.068

T;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.85

.;P

Vest4

0.091

MutPred

0.43

.;Gain of disorder (P = 0.0431);

MVP

0.19

MPC

0.10

ClinPred

0.14

GERP RS

1.1

Varity_R

0.033

gMVP

0.026

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

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