Variant 7-149847948-T-C 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_001099220.3(ZNF862):c.455T>C(p.Met152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,608,574 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ZNF862
NM_001099220.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.117

Variant links:

Genes affected

ZNF862 (HGNC:34519): (zinc finger protein 862) Predicted to enable metal ion binding activity and protein dimerization activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF862 links:

Genome browser will be placed here

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=0.013451308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF862	NM_001099220.3 linkuse as main transcript	c.455T>C	p.Met152Thr	missense_variant	4/8	ENST00000223210.5	NP_001092690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF862	ENST00000223210.5 linkuse as main transcript	c.455T>C	p.Met152Thr	missense_variant	4/8	5	NM_001099220.3	ENSP00000223210	P1	O60290-1
ZNF862	ENST00000460379.1 linkuse as main transcript	c.203T>C	p.Met68Thr	missense_variant	4/4	4		ENSP00000417450

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00130

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000101

AC:

AN:

238038

Hom.:

AF XY:

0.0000542

AC XY:

AN XY:

129084

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.000150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1456274

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723916

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.000114

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000381

AC:

AN:

152300

Hom.:

Cov.:

AF XY:

0.000362

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000809

Hom.:

Bravo

AF:

0.000487

ESP6500AA

AF:

0.00175

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000910

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

Jul 06, 2021

The c.455T>C (p.M152T) alteration is located in exon 4 (coding exon 4) of the ZNF862 gene. This alteration results from a T to C substitution at nucleotide position 455, causing the methionine (M) at amino acid position 152 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

Benign

0.092

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.3

DANN

Benign

0.31

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0034

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.1

N;D

REVEL

Benign

0.012

Sift

Benign

0.098

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.0

B;.

Vest4

0.20

MVP

0.030

MPC

0.19

ClinPred

0.0028

GERP RS

0.21

Varity_R

0.10

gMVP

0.18

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