Variant 7-149847936-C-T 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.443C>T(p.Pro148Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,606,664 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 1 hom. )

Consequence

ZNF862
NM_001099220.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

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=0.034695864).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF862	NM_001099220.3 linkuse as main transcript	c.443C>T	p.Pro148Leu	missense_variant	4/8	ENST00000223210.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF862	ENST00000223210.5 linkuse as main transcript	c.443C>T	p.Pro148Leu	missense_variant	4/8	5	NM_001099220.3	P1	O60290-1
ZNF862	ENST00000460379.1 linkuse as main transcript	c.191C>T	p.Pro64Leu	missense_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.000394

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000342

AC:

AN:

233756

Hom.:

AF XY:

0.000284

AC XY:

AN XY:

126728

show subpopulations

Gnomad AFR exome

AF:

0.000142

Gnomad AMR exome

AF:

0.0000305

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.000410

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.000413

AC:

601

AN:

1454406

Hom.:

Cov.:

AF XY:

0.000387

AC XY:

280

AN XY:

722816

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000231

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00164

Gnomad4 NFE exome

AF:

0.000444

Gnomad4 OTH exome

AF:

0.000299

GnomAD4 genome

AF:

0.000394

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000482

Hom.:

Bravo

AF:

0.000283

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.000722

AC:

ExAC

AF:

0.000331

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

Aug 12, 2021

The c.443C>T (p.P148L) alteration is located in exon 4 (coding exon 4) of the ZNF862 gene. This alteration results from a C to T substitution at nucleotide position 443, causing the proline (P) at amino acid position 148 to be replaced by a leucine (L). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.24

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

0.074

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.5

D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;.

Vest4

0.58

MVP

0.067

MPC

0.69

ClinPred

0.30

GERP RS

4.4

Varity_R

0.33

gMVP

0.28

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