Variant 16-30524740-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024671.4(ZNF768):c.1400A>G(p.Asn467Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000187 in 1,592,080 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

ZNF768
NM_024671.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.63

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055425107).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF768	NM_024671.4 linkuse as main transcript	c.1400A>G	p.Asn467Ser	missense_variant	2/2	ENST00000380412.7	NP_078947.3
ZNF768	XM_017023665.3 linkuse as main transcript	c.1472A>G	p.Asn491Ser	missense_variant	2/2		XP_016879154.1
ZNF768	XM_017023666.2 linkuse as main transcript	c.1307A>G	p.Asn436Ser	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.1400A>G	p.Asn467Ser	missense_variant	2/2	1	NM_024671.4	ENSP00000369777	P2
ZNF768	ENST00000562803.1 linkuse as main transcript	c.1307A>G	p.Asn436Ser	missense_variant	2/2	3		ENSP00000456527	A2

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

146322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000338

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000197

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

247872

Hom.:

AF XY:

0.000164

AC XY:

AN XY:

134384

show subpopulations

Gnomad AFR exome

AF:

0.0000624

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000187

AC:

271

AN:

1445628

Hom.:

Cov.:

AF XY:

0.000192

AC XY:

138

AN XY:

718910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.000238

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000453

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

AF:

0.000184

AC:

AN:

146452

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71650

show subpopulations

Gnomad4 AFR

AF:

0.000177

Gnomad4 AMR

AF:

0.000337

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000197

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000174

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000298

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

Oct 06, 2021

The c.1400A>G (p.N467S) alteration is located in exon 2 (coding exon 2) of the ZNF768 gene. This alteration results from a A to G substitution at nucleotide position 1400, causing the asparagine (N) at amino acid position 467 to be replaced by a serine (S). 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

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0073

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.27

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.055

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.84

N;.

MutationTaster

Benign

0.76

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.26

N;.

REVEL

Benign

0.092

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.81

P;.

Vest4

0.25

MVP

0.26

MPC

1.4

ClinPred

0.13

GERP RS

3.6

Varity_R

0.024

gMVP

0.15

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