Variant 7-149176570-G-A 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_170686.3(ZNF398):c.764G>A(p.Ser255Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000542 in 1,604,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 0 hom. )

Consequence

ZNF398
NM_170686.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

ZNF398 (HGNC:18373): (zinc finger protein 398) This gene encodes a member of the Kruppel family of C2H2-type zinc-finger transcription factor proteins. The encoded protein acts as a transcriptional activator. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described, but their full length sequence has not been determined. [provided by RefSeq, Jul 2008]

ZNF398 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=0.014669001).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF398	NM_170686.3 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	5/6	ENST00000475153.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF398	ENST00000475153.6 linkuse as main transcript	c.764G>A	p.Ser255Asn	missense_variant	5/6	1	NM_170686.3	P1	Q8TD17-1
ZNF398	ENST00000426851.6 linkuse as main transcript	c.251G>A	p.Ser84Asn	missense_variant	6/7	1			Q8TD17-2
ZNF398	ENST00000483892.5 linkuse as main transcript	c.251G>A	p.Ser84Asn	missense_variant	5/6	5			Q8TD17-2
ZNF398	ENST00000491174.1 linkuse as main transcript	c.251G>A	p.Ser84Asn	missense_variant	6/7	2			Q8TD17-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000315

AC:

AN:

244614

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

132366

show subpopulations

Gnomad AFR exome

AF:

0.000310

Gnomad AMR exome

AF:

0.000246

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000930

Gnomad NFE exome

AF:

0.000536

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.000568

AC:

825

AN:

1452478

Hom.:

Cov.:

AF XY:

0.000551

AC XY:

398

AN XY:

722970

show subpopulations

Gnomad4 AFR exome

AF:

0.000152

Gnomad4 AMR exome

AF:

0.000188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000938

Gnomad4 NFE exome

AF:

0.000693

Gnomad4 OTH exome

AF:

0.000601

GnomAD4 genome

AF:

0.000289

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000481

Hom.:

Bravo

AF:

0.000295

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000321

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000534

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

Feb 17, 2022

The c.764G>A (p.S255N) alteration is located in exon 5 (coding exon 5) of the ZNF398 gene. This alteration results from a G to A substitution at nucleotide position 764, causing the serine (S) at amino acid position 255 to be replaced by an asparagine (N). 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

0.12

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.79

Cadd

Benign

Dann

Benign

0.93

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.0050

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.58

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.23

T;T;T;T

Sift4G

Benign

0.28

T;T;T;T

Polyphen

0.072

.;B;.;.

Vest4

0.13

MVP

0.20

MPC

0.28

ClinPred

0.0042

GERP RS

2.5

Varity_R

0.026

gMVP

0.31

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