Variant 9-113876391-C-G 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_001318042.2(ZNF618):c.11C>G(p.Pro4Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000585 in 1,197,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P4L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ZNF618
NM_001318042.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

ZNF618 (HGNC:29416): (zinc finger protein 618) Enables identical protein binding activity and transcription coregulator binding activity. Involved in positive regulation of chromatin binding activity. Located in chromatin. Part of pericentric heterochromatin. [provided by Alliance of Genome Resources, Apr 2022]

ZNF618 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=0.19404238).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF618	NM_001318042.2 linkuse as main transcript	c.11C>G	p.Pro4Arg	missense_variant	1/15	ENST00000374126.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF618	ENST00000374126.10 linkuse as main transcript	c.11C>G	p.Pro4Arg	missense_variant	1/15	1	NM_001318042.2	P4	Q5T7W0-1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1047136

Hom.:

Cov.:

AF XY:

0.00000202

AC XY:

AN XY:

494058

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000138

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:

0.00000111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149968

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000604

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

Aug 02, 2021

The c.11C>G (p.P4R) alteration is located in exon 1 (coding exon 1) of the ZNF618 gene. This alteration results from a C to G substitution at nucleotide position 11, causing the proline (P) at amino acid position 4 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

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.;.;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.69

T;T;T;T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.19

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;.;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.46

N;.;N;N;N

REVEL

Benign

0.053

Sift

Pathogenic

0.0

D;.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

0.57

P;.;D;.;D

Vest4

0.24

MutPred

0.26

Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);

MVP

0.043

MPC

1.4

ClinPred

0.75

GERP RS

0.64

Varity_R

0.15

gMVP

0.29

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