Variant 2-179445560-T-G 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.1130A>C(p.Gln377Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,910 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZNF385B
NM_152520.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF385B	NM_152520.6 link	c.1130A>C	p.Gln377Pro	missense_variant	8/10	ENST00000410066.7	NP_689733.4	Q569K4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF385B	ENST00000410066.7 link	c.1130A>C	p.Gln377Pro	missense_variant	8/10	1	NM_152520.6	ENSP00000386845.2		A0A2U3TZT0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247162

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133536

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458910

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725554

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Nov 20, 2024

The c.1085A>C (p.Q362P) alteration is located in exon 8 (coding exon 6) of the ZNF385B gene. This alteration results from a A to C substitution at nucleotide position 1085, causing the glutamine (Q) at amino acid position 362 to be replaced by a proline (P). 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

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

.;.;.;.;T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

D;.;D;D;D;D

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.9

.;.;.;.;M;.

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-6.0

.;D;D;D;.;D

REVEL

Uncertain

0.56

Sift

Pathogenic

0.0

.;D;D;D;.;D

Sift4G

Pathogenic

0.0

.;D;D;D;.;D

Polyphen

1.0, 0.88

.;.;D;.;P;.

Vest4

0.87, 0.88, 0.87

MutPred

0.68

.;.;.;.;Loss of MoRF binding (P = 0.0618);.;

MVP

0.57

MPC

0.84

ClinPred

0.99

GERP RS

6.0

Varity_R

0.94

gMVP

0.92

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