Variant 19-53408424-G-A 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_001040185.3(ZNF765):c.869G>A(p.Arg290His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. R290C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZNF765
NM_001040185.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.192

Variant links:

Genes affected

ZNF765 (HGNC:25092): (zinc finger protein 765) 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]

ZNF765 links:

ZNF765-ZNF761 (HGNC:):

ZNF765-ZNF761 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=0.038743407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF765	NM_001040185.3 linkuse as main transcript	c.869G>A	p.Arg290His	missense_variant	4/4	ENST00000396408.8
ZNF765-ZNF761	NM_001350496.2 linkuse as main transcript	c.-1345+6233G>A		intron_variant
ZNF765	NM_001350495.2 linkuse as main transcript	c.710G>A	p.Arg237His	missense_variant	3/3
ZNF765	NR_146721.2 linkuse as main transcript	n.260+6233G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF765	ENST00000396408.8 linkuse as main transcript	c.869G>A	p.Arg290His	missense_variant	4/4	1	NM_001040185.3	P1	Q7L2R6-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000968

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:

0.0000946

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251204

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461806

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151850

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74170

show subpopulations

Gnomad4 AFR

AF:

0.0000968

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000946

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

Dec 08, 2023

The c.869G>A (p.R290H) alteration is located in exon 4 (coding exon 3) of the ZNF765 gene. This alteration results from a G to A substitution at nucleotide position 869, causing the arginine (R) at amino acid position 290 to be replaced by a histidine (H). 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

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

Cadd

Benign

1.8

Dann

Benign

0.65

DEOGEN2

Benign

0.0040

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.12

M_CAP

Benign

0.0015

MetaRNN

Benign

0.039

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.47

REVEL

Benign

0.030

Sift

Benign

0.36

Sift4G

Benign

0.50

Polyphen

0.0060

Vest4

0.018

MVP

0.067

MPC

0.053

ClinPred

0.035

GERP RS

-0.35

Varity_R

0.016

gMVP

0.020

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