Genetic Variant ZNF766:p.Arg5Gln (chr19-52269627-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001010851.3(ZNF766):c.14G>A(p.Arg5Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5P) has been classified as Uncertain significance.

Frequency

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

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZNF766
NM_001010851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.121

Variant links:

Genes affected

ZNF766 (HGNC:28063): (zinc finger protein 766) Predicted to enable DNA binding activity and metal ion binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF766 links:

LOC124904763 (HGNC:):

LOC124904763 links:

Genome browser will be placed here

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=0.11327672).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF766	NM_001010851.3 link	c.14G>A	p.Arg5Gln	missense_variant	Exon 1 of 4	ENST00000439461.6	NP_001010851.1	Q5HY98
LOC124904763	XR_007067331.1 link	n.986C>T		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZNF766	ENST00000439461.6 link	c.14G>A	p.Arg5Gln	missense_variant	Exon 1 of 4	1	NM_001010851.3	ENSP00000409652.1	Q5HY98
ZNF766	ENST00000599581.5 link	c.14G>A	p.Arg5Gln	missense_variant	Exon 1 of 5	2		ENSP00000471965.1	A0A0B4J2B2
ZNF766	ENST00000593703 link	c.-37G>A		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000469186.1	M0QXI4
ZNF766	ENST00000601711 link	c.-330G>A		5_prime_UTR_variant	Exon 1 of 4	5		ENSP00000472743.1	M0R2R1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

247986

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460538

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726670

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:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000992

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14G>A (p.R5Q) alteration is located in exon 1 (coding exon 1) of the ZNF766 gene. This alteration results from a G to A substitution at nucleotide position 14, causing the arginine (R) at amino acid position 5 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.075

N;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.20

N;.

REVEL

Benign

0.040

Sift

Uncertain

0.023

D;.

Sift4G

Benign

0.25

T;T

Polyphen

0.92

P;.

Vest4

0.35

MutPred

0.36

Loss of MoRF binding (P = 0.0067);Loss of MoRF binding (P = 0.0067);

MVP

0.24

MPC

0.052

ClinPred

0.21

GERP RS

2.0

Varity_R

0.075

gMVP

0.033

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