Variant 16-30525829-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_024671.4(ZNF768):c.311G>T(p.Ser104Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,534,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.139

Variant links:

Genes affected

ZNF768 (HGNC:26273): (zinc finger protein 768) Enables RNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF768 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity ZN768_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051977992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF768	NM_024671.4 linkuse as main transcript	c.311G>T	p.Ser104Ile	missense_variant	2/2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3 linkuse as main transcript	c.383G>T	p.Ser128Ile	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2 linkuse as main transcript	c.218G>T	p.Ser73Ile	missense_variant	2/2		XP_016879155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF768	ENST00000380412.7 linkuse as main transcript	c.311G>T	p.Ser104Ile	missense_variant	2/2	1	NM_024671.4	ENSP00000369777	P2
ZNF768	ENST00000562803.1 linkuse as main transcript	c.218G>T	p.Ser73Ile	missense_variant	2/2	3		ENSP00000456527	A2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152018

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000182

AC:

AN:

181492

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

96472

show subpopulations

Gnomad AFR exome

AF:

0.0000695

Gnomad AMR exome

AF:

0.000279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000635

Gnomad FIN exome

AF:

0.0000572

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.000485

GnomAD4 exome

AF:

0.000111

AC:

154

AN:

1382448

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

680524

show subpopulations

Gnomad4 AFR exome

AF:

0.0000656

Gnomad4 AMR exome

AF:

0.000231

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000697

Gnomad4 FIN exome

AF:

0.0000398

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

AF:

0.000145

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74236

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:

0.0000945

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000166

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

Sep 30, 2022

The c.311G>T (p.S104I) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a G to T substitution at nucleotide position 311, causing the serine (S) at amino acid position 104 to be replaced by an isoleucine (I). 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

-0.38

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

0.56

D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.87

N;.

REVEL

Benign

0.061

Sift

Uncertain

0.014

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.24

B;.

Vest4

0.31

MVP

0.13

MPC

0.85

ClinPred

0.021

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.79

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