Variant chr19-52950277-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001202457.3(ZNF816):c.1498C>G(p.His500Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,613,600 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

ZNF816
NM_001202457.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.507

Variant links:

Genes affected

ZNF816 (HGNC:26995): (zinc finger protein 816) 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 integral component of membrane. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF816 links:

ZNF816-ZNF321P (HGNC:):

ZNF816-ZNF321P links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008083284).

BP6

Variant 19-52950277-G-C is Benign according to our data. Variant chr19-52950277-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 773361.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF816	NM_001202457.3 linkuse as main transcript	c.1498C>G	p.His500Asp	missense_variant	4/4	ENST00000444460.7	NP_001189386.1
ZNF816-ZNF321P	NM_001202473.2 linkuse as main transcript	c.190+2474C>G		intron_variant			NP_001189402.1
ZNF816	NM_001031665.4 linkuse as main transcript	c.1498C>G	p.His500Asp	missense_variant	5/5		NP_001026835.1
ZNF816	NM_001202456.3 linkuse as main transcript	c.1498C>G	p.His500Asp	missense_variant	4/4		NP_001189385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF816	ENST00000444460.7 linkuse as main transcript	c.1498C>G	p.His500Asp	missense_variant	4/4	1	NM_001202457.3	ENSP00000403266	P1
ZNF816	ENST00000357666.8 linkuse as main transcript	c.1498C>G	p.His500Asp	missense_variant	5/5	1		ENSP00000350295	P1

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

156

AN:

151704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.000190

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00127

AC:

318

AN:

251350

Hom.:

AF XY:

0.00129

AC XY:

175

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00116

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00123

AC:

1794

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

925

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00114

Gnomad4 ASJ exome

AF:

0.00321

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.00103

AC:

156

AN:

151828

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.000242

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000417

Gnomad4 FIN

AF:

0.000190

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00154

Hom.:

Bravo

AF:

0.00114

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00128

AC:

155

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.25

LIST_S2

Uncertain

0.90

.;D

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0081

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.66

N;N

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.045

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.080

T;T

Polyphen

0.76

P;P

Vest4

0.13

MVP

0.18

MPC

0.17

ClinPred

0.066

GERP RS

1.9

Varity_R

0.24

gMVP

0.11

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