Variant 2-179444941-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152520.6(ZNF385B):c.1177G>A(p.Gly393Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF385B
NM_152520.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

Variant links:

Genes affected

ZNF385B (HGNC:26332): (zinc finger protein 385B) Enables p53 binding activity. Involved in intrinsic apoptotic signaling pathway by p53 class mediator. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF385B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385B	NM_152520.6 linkuse as main transcript	c.1177G>A	p.Gly393Arg	missense_variant	9/10	ENST00000410066.7	NP_689733.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385B	ENST00000410066.7 linkuse as main transcript	c.1177G>A	p.Gly393Arg	missense_variant	9/10	1	NM_152520.6	ENSP00000386845	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251494

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000752

AC:

AN:

1461818

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

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

Apr 05, 2023

The c.1132G>A (p.G378R) alteration is located in exon 9 (coding exon 7) of the ZNF385B gene. This alteration results from a G to A substitution at nucleotide position 1132, causing the glycine (G) at amino acid position 378 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

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

.;.;.;.;T

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;.;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.80

D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.4

.;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-8.0

.;D;D;D;.

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

.;D;D;D;.

Sift4G

Pathogenic

0.0

.;D;D;D;.

Polyphen

1.0

.;.;D;.;D

Vest4

0.57, 0.59, 0.57

MutPred

0.37

.;.;.;.;Gain of solvent accessibility (P = 0.0456);

MVP

0.61

MPC

0.83

ClinPred

0.98

GERP RS

4.6

Varity_R

0.81

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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