9-113969139-G-A

Variant summary

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

The NM_001318042.2(ZNF618):​c.56G>A​(p.Gly19Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,698 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 (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZNF618
NM_001318042.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.45
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]

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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=0.25979376).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF618NM_001318042.2 linkuse as main transcriptc.56G>A p.Gly19Glu missense_variant 2/15 ENST00000374126.10 NP_001304971.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF618ENST00000374126.10 linkuse as main transcriptc.56G>A p.Gly19Glu missense_variant 2/151 NM_001318042.2 ENSP00000363241 P4Q5T7W0-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249178
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135180
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000869
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:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461698
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000894
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1

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 submitterclinical testingAmbry GeneticsMar 18, 2024The c.56G>A (p.G19E) alteration is located in exon 2 (coding exon 2) of the ZNF618 gene. This alteration results from a G to A substitution at nucleotide position 56, causing the glycine (G) at amino acid position 19 to be replaced by a glutamic acid (E). 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
-0.083
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.027
T;.;.;T;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
T;T;T;T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.26
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;N;N;.;.
MutationTaster
Benign
0.93
D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
0.080
N;.;N;N;N
REVEL
Benign
0.21
Sift
Uncertain
0.012
D;.;D;D;D
Sift4G
Benign
0.84
T;T;T;T;T
Polyphen
1.0
D;.;D;.;D
Vest4
0.61
MutPred
0.26
Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);Gain of helix (P = 0.0117);
MVP
0.20
MPC
1.5
ClinPred
0.83
D
GERP RS
5.0
Varity_R
0.14
gMVP
0.23

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.

Other links and lift over

dbSNP: rs746472178; hg19: chr9-116731419; API