Variant 19-52950609-A-G 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_001202457.3(ZNF816):c.1166T>C(p.Ile389Thr) 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 1,461,708 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF816
NM_001202457.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.13

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 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=0.04731527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZNF816	NM_001202457.3 linkuse as main transcript	c.1166T>C	p.Ile389Thr	missense_variant	4/4	ENST00000444460.7
ZNF816-ZNF321P	NM_001202473.2 linkuse as main transcript	c.190+2142T>C		intron_variant
ZNF816	NM_001031665.4 linkuse as main transcript	c.1166T>C	p.Ile389Thr	missense_variant	5/5
ZNF816	NM_001202456.3 linkuse as main transcript	c.1166T>C	p.Ile389Thr	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF816	ENST00000444460.7 linkuse as main transcript	c.1166T>C	p.Ile389Thr	missense_variant	4/4	1	NM_001202457.3	P1
ZNF816	ENST00000357666.8 linkuse as main transcript	c.1166T>C	p.Ile389Thr	missense_variant	5/5	1		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727154

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000301

Hom.:

ExAC

AF:

0.0000247

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

Jan 29, 2024

The c.1166T>C (p.I389T) alteration is located in exon 5 (coding exon 3) of the ZNF816 gene. This alteration results from a T to C substitution at nucleotide position 1166, causing the isoleucine (I) at amino acid position 389 to be replaced by a threonine (T). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.056

DANN

Benign

0.59

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0096

M_CAP

Benign

0.00066

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.48

N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.61

N;N

REVEL

Benign

0.013

Sift

Benign

0.21

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.047

B;B

Vest4

0.050

MutPred

0.55

Gain of disorder (P = 0.0151);Gain of disorder (P = 0.0151);

MVP

0.030

MPC

0.15

ClinPred

0.11

GERP RS

-2.5

Varity_R

0.021

gMVP

0.011

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