Variant chr19-52705418-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001161499.2(ZNF611):c.1637C>G(p.Ala546Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

ZNF611
NM_001161499.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.75

Variant links:

Genes affected

ZNF611 (HGNC:28766): (zinc finger protein 611) 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]

ZNF611 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050284892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF611	NM_001161499.2 link	c.1637C>G	p.Ala546Gly	missense_variant	6/6	ENST00000652185.1	NP_001154971.1	Q8N823-1
ZNF611	NM_001161500.2 link	c.1637C>G	p.Ala546Gly	missense_variant	5/5		NP_001154972.1	Q8N823-1
ZNF611	NM_030972.3 link	c.1637C>G	p.Ala546Gly	missense_variant	7/7		NP_112234.3	Q8N823-1
ZNF611	NM_001161501.1 link	c.1430C>G	p.Ala477Gly	missense_variant	5/5		NP_001154973.1	Q8N823-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF611	ENST00000652185.1 link	c.1637C>G	p.Ala546Gly	missense_variant	6/6		NM_001161499.2	ENSP00000498713.1		Q8N823-1

Frequencies

GnomAD3 genomes

AF:

0.000256

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.000514

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

251448

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000378

AC:

552

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000370

AC XY:

269

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000313

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:

0.000441

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000256

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000283

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000514

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000419

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000533

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

Jan 23, 2024

The c.1637C>G (p.A546G) alteration is located in exon 7 (coding exon 3) of the ZNF611 gene. This alteration results from a C to G substitution at nucleotide position 1637, causing the alanine (A) at amino acid position 546 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

0.15

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.2

DANN

Uncertain

0.98

DEOGEN2

Benign

0.036

.;T;T;.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0039

LIST_S2

Uncertain

0.91

D;.;D;.;.;.

M_CAP

Benign

0.00084

MetaRNN

Benign

0.050

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.68

.;N;N;.;N;.

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.7

D;D;D;.;D;.

REVEL

Benign

0.051

Sift

Benign

0.074

T;T;T;.;T;.

Sift4G

Benign

0.074

T;T;T;T;T;T

Polyphen

0.041

.;B;B;.;B;.

Vest4

0.096

MVP

0.067

MPC

0.12

ClinPred

0.045

GERP RS

0.14

Varity_R

0.082

gMVP

0.014

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