Variant 2-179443336-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152520.6(ZNF385B):c.1375G>T(p.Ala459Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF385B
NM_152520.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.106909394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF385B	NM_152520.6 linkuse as main transcript	c.1375G>T	p.Ala459Ser	missense_variant	10/10	ENST00000410066.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF385B	ENST00000410066.7 linkuse as main transcript	c.1375G>T	p.Ala459Ser	missense_variant	10/10	1	NM_152520.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249514

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460028

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 18, 2023

The c.1330G>T (p.A444S) alteration is located in exon 10 (coding exon 8) of the ZNF385B gene. This alteration results from a G to T substitution at nucleotide position 1330, causing the alanine (A) at amino acid position 444 to be replaced by a serine (S). 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

Benign

-0.39

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.012

.;.;.;.;T

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.84

T;.;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

.;.;.;.;L

MutationTaster

Benign

0.88

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.1

.;N;N;N;.

REVEL

Benign

0.035

Sift

Benign

0.15

.;T;T;T;.

Sift4G

Benign

0.50

.;T;T;T;.

Polyphen

0.020, 0.0030

.;.;B;.;B

Vest4

0.15, 0.14, 0.13

MutPred

0.21

.;.;.;.;Gain of glycosylation at A444 (P = 0.0035);

MVP

0.15

MPC

0.19

ClinPred

0.18

GERP RS

4.6

Varity_R

0.11

gMVP

0.51

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