dbSNP rs763139069: ZNF397:p.Arg50Ser (chr18-35242618-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001135178.3(ZNF397):c.148C>A(p.Arg50Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R50C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF397
NM_001135178.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.650

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.923

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF397	NM_001135178.3 link	c.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 4	ENST00000330501.12	NP_001128650.1	Q8NF99-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF397	ENST00000330501.12 link	c.148C>A	p.Arg50Ser	missense_variant	Exon 2 of 4	1	NM_001135178.3	ENSP00000331577.6		Q8NF99-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251362

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T;.;.;.;T

Eigen

Pathogenic

0.79

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.73

T;.;T;T;T;T;T

M_CAP

Benign

0.039

MetaRNN

Pathogenic

0.92

D;D;D;D;D;D;D

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.7

.;H;H;H;.;H;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.4

.;.;D;D;D;.;.

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;.;D;D;D;.;.

Sift4G

Uncertain

0.0030

D;D;D;D;D;D;D

Polyphen

1.0, 1.0, 1.0

.;D;D;D;D;D;.

Vest4

0.80, 0.78, 0.80, 0.81, 0.80, 0.80

MutPred

0.90

Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);Gain of ubiquitination at K55 (P = 0.0477);

MVP

0.23

MPC

0.69

ClinPred

0.99

GERP RS

4.2

Varity_R

0.71

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over