Variant 8-28351802-G-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_018660.3(ZNF395):c.926C>T(p.Thr309Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000661 in 1,542,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

ZNF395
NM_018660.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

Variant links:

Genes affected

ZNF395 (HGNC:18737): (zinc finger protein 395) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

ZNF395 links:

FBXO16 (HGNC:13618): (F-box protein 16) This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbx class. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

FBXO16 links:

Genome browser will be placed here

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=0.19195175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF395	NM_018660.3 link	c.926C>T	p.Thr309Ile	missense_variant	7/10	ENST00000344423.10	NP_061130.1	Q9H8N7Q7L9C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF395	ENST00000344423.10 link	c.926C>T	p.Thr309Ile	missense_variant	7/10	1	NM_018660.3	ENSP00000340494.5		Q9H8N7

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152204

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000651

AC:

AN:

199762

Hom.:

AF XY:

0.0000749

AC XY:

AN XY:

106788

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:

0.000127

Gnomad OTH exome

AF:

0.000202

GnomAD4 exome

AF:

0.0000676

AC:

AN:

1390696

Hom.:

Cov.:

AF XY:

0.0000731

AC XY:

AN XY:

684078

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:

0.0000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000816

Gnomad4 OTH exome

AF:

0.0000865

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74346

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000120

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000248

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

Oct 16, 2024

The c.926C>T (p.T309I) alteration is located in exon 7 (coding exon 6) of the ZNF395 gene. This alteration results from a C to T substitution at nucleotide position 926, causing the threonine (T) at amino acid position 309 to be replaced by an isoleucine (I). 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

0.21

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.66

.;.;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

L;L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.050

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.19

T;T;T

Polyphen

0.93

P;P;P

Vest4

0.30

MVP

0.10

MPC

0.65

ClinPred

0.13

GERP RS

4.1

Varity_R

0.095

gMVP

0.14

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