Variant 7-149147765-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_170686.3(ZNF398):c.23C>G(p.Pro8Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,390,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

ZNF398
NM_170686.3 missense, splice_region

Scores

Splicing: ADA: 0.0009094

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.693

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:

ZNF398 (HGNC:):

ZNF398 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3740303).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF398	NM_170686.3 linkuse as main transcript	c.23C>G	p.Pro8Arg	missense_variant, splice_region_variant	1/6	ENST00000475153.6	NP_733787.1	Q8TD17-1A0A090N7S8
ZNF398	XM_011516440.3 linkuse as main transcript	c.-516C>G		5_prime_UTR_variant	1/6		XP_011514742.1
ZNF398	NM_020781.4 linkuse as main transcript	c.-489-6180C>G		intron_variant			NP_065832.1	Q8TD17-2A0A090N8F2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF398	ENST00000475153.6 linkuse as main transcript	c.23C>G	p.Pro8Arg	missense_variant, splice_region_variant	1/6	1	NM_170686.3	ENSP00000420418.1	Q8TD17-1
ZNF398	ENST00000426851.6 linkuse as main transcript	c.-489-6180C>G		intron_variant		1		ENSP00000389972.2	Q8TD17-2
ZNF398	ENST00000485111.5 linkuse as main transcript	n.135+523C>G		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000630

AC:

AN:

1238694

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

608260

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000645

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000758

Gnomad4 OTH exome

AF:

0.0000199

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152124

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Oct 12, 2024

The c.23C>G (p.P8R) alteration is located in exon 1 (coding exon 1) of the ZNF398 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the proline (P) at amino acid position 8 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.028

Eigen

Benign

0.11

Eigen_PC

Benign

0.078

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.49

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.70

REVEL

Benign

0.17

Sift

Benign

0.26

Sift4G

Benign

0.89

Polyphen

1.0

Vest4

0.43

MutPred

0.15

Loss of glycosylation at P8 (P = 0.0421);

MVP

0.47

MPC

0.33

ClinPred

0.58

GERP RS

4.0

Varity_R

0.078

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00091

dbscSNV1_RF

Benign

0.040

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