Variant 18-35246165-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001135178.3(ZNF397):c.1460G>A(p.Gly487Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000587 in 1,551,956 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 3 hom. )

Consequence

ZNF397
NM_001135178.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.12

Variant links:

Genes affected

ZNF397 (HGNC:18818): (zinc finger protein 397) This gene encodes a protein with a N-terminal SCAN domain, and the longer isoform contains nine C2H2-type zinc finger repeats in the C-terminal domain. The protein localizes to centromeres during interphase and early prophase, and different isoforms can repress or activate transcription in transfection studies. Multiple transcript variants encoding different isoforms have been found for this gene. Additional variants have been described, but their biological validity has not been determined. [provided by RefSeq, Oct 2009]

ZNF397 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3324553).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF397	NM_001135178.3 linkuse as main transcript	c.1460G>A	p.Gly487Asp	missense_variant	4/4	ENST00000330501.12	NP_001128650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF397	ENST00000330501.12 linkuse as main transcript	c.1460G>A	p.Gly487Asp	missense_variant	4/4	1	NM_001135178.3	ENSP00000331577	P1	Q8NF99-1

Frequencies

GnomAD3 genomes

AF:

0.000532

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000970

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000383

AC:

AN:

159390

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

83878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000201

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000175

Gnomad FIN exome

AF:

0.0000589

Gnomad NFE exome

AF:

0.000805

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.000593

AC:

830

AN:

1399700

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

418

AN XY:

690342

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000840

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000215

Gnomad4 FIN exome

AF:

0.000202

Gnomad4 NFE exome

AF:

0.000702

Gnomad4 OTH exome

AF:

0.000689

GnomAD4 genome

AF:

0.000532

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.000970

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000732

Hom.:

Bravo

AF:

0.000332

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.000159

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 11, 2021

The c.1460G>A (p.G487D) alteration is located in exon 4 (coding exon 3) of the ZNF397 gene. This alteration results from a G to A substitution at nucleotide position 1460, causing the glycine (G) at amino acid position 487 to be replaced by an aspartic acid (D). 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

0.61

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.25

M_CAP

Benign

0.048

MetaRNN

Benign

0.33

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.93

D;D;D;D

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.29

Sift

Uncertain

0.012

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.62

MVP

0.099

MPC

0.74

ClinPred

0.18

GERP RS

3.4

Varity_R

0.39

gMVP

0.12

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