Variant 16-89222118-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001201407.2(ZNF778):c.52T>G(p.Cys18Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,451,264 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: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF778
NM_001201407.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

Variant links:

Genes affected

ZNF778 (HGNC:26479): (zinc finger protein 778) The protein encoded by this gene is a member of the krueppel C2H2-type zinc-finger protein family, and it contains one KRAB domain and eighteen C2H2-type zinc fingers. This gene is a candidate gene for autism and variable cognitive impairment in the 16q24.3 microdeletion syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2011]

ZNF778 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19683936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF778	NM_001201407.2 link	c.52T>G	p.Cys18Gly	missense_variant	3/7	ENST00000433976.7	NP_001188336.1	A0A0A0MSW5
ZNF778	NM_001378881.1 link	c.52T>G	p.Cys18Gly	missense_variant	3/7		NP_001365810.1
ZNF778	NM_182531.5 link	c.52T>G	p.Cys18Gly	missense_variant	3/6		NP_872337.2	Q96MU6-1
ZNF778	NR_037705.3 link	n.391T>G		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF778	ENST00000433976.7 link	c.52T>G	p.Cys18Gly	missense_variant	3/7	5	NM_001201407.2	ENSP00000405289.3		A0A0A0MSW5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

243780

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132474

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000230

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1451264

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000769

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 09, 2023

The c.52T>G (p.C18G) alteration is located in exon 3 (coding exon 2) of the ZNF778 gene. This alteration results from a T to G substitution at nucleotide position 52, causing the cysteine (C) at amino acid position 18 to be replaced by a glycine (G). 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

0.084

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.9

DANN

Benign

0.78

DEOGEN2

Benign

0.0064

.;.;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.33

T;T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

.;.;L

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.7

D;D;.

REVEL

Benign

0.14

Sift

Benign

0.12

T;D;.

Sift4G

Benign

0.13

T;D;D

Polyphen

0.90

.;.;P

Vest4

0.39

MutPred

0.65

Gain of disorder (P = 0.0022);Gain of disorder (P = 0.0022);Gain of disorder (P = 0.0022);

MVP

0.43

MPC

0.0047

ClinPred

0.12

GERP RS

0.90

Varity_R

0.070

gMVP

0.041

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