Variant 6-43337330-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014345.3(ZNF318):c.6668T>C(p.Leu2223Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000997 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 0 hom. )

Consequence

ZNF318
NM_014345.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

ZNF318 (HGNC:13578): (zinc finger protein 318) Predicted to enable protein heterodimerization activity and protein homodimerization activity. Predicted to be involved in negative regulation of transcription, DNA-templated and positive regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF318 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012259185).

BP6

Variant 6-43337330-A-G is Benign according to our data. Variant chr6-43337330-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2260365.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF318	NM_014345.3 linkuse as main transcript	c.6668T>C	p.Leu2223Pro	missense_variant	10/10	ENST00000361428.3	NP_055160.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF318	ENST00000361428.3 linkuse as main transcript	c.6668T>C	p.Leu2223Pro	missense_variant	10/10	1	NM_014345.3	ENSP00000354964	P1	Q5VUA4-1
ZNF318	ENST00000605935.5 linkuse as main transcript	c.3276+5346T>C		intron_variant, NMD_transcript_variant		1		ENSP00000475748		Q5VUA4-2
ZNF318	ENST00000606599.1 linkuse as main transcript	c.161+5346T>C		intron_variant		2		ENSP00000475511

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000538

AC:

135

AN:

250956

Hom.:

AF XY:

0.000546

AC XY:

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.000981

GnomAD4 exome

AF:

0.00104

AC:

1526

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

738

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00130

Gnomad4 OTH exome

AF:

0.000960

GnomAD4 genome

AF:

0.000545

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000831

Hom.:

Bravo

AF:

0.000548

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000502

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.019

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.42

M_CAP

Benign

0.0029

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.3

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.25

REVEL

Benign

0.029

Sift

Benign

0.31

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.073

MVP

0.29

MPC

0.10

ClinPred

0.0099

GERP RS

0.68

Varity_R

0.077

gMVP

0.088

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