9-113988507-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318042.2(ZNF618):c.264C>G(p.Ser88Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ZNF618 NM_001318042.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.584

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]

ACMG classification

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=0.13742155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF618	NM_001318042.2	c.264C>G	p.Ser88Arg	missense_variant	3/15	ENST00000374126.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF618	ENST00000374126.10	c.264C>G	p.Ser88Arg	missense_variant	3/15	1	NM_001318042.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.264C>G (p.S88R) alteration is located in exon 3 (coding exon 3) of the ZNF618 gene. This alteration results from a C to G substitution at nucleotide position 264, causing the serine (S) at amino acid position 88 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	0.22
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.053	T;.;.;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.87	D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.0	N;.;N;N;N
REVEL	Benign	0.092
Sift	Benign	0.085	T;.;T;T;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.65	P;.;B;.;B
Vest4		0.33
MutPred		0.33		Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);Loss of loop (P = 0.0288);
MVP		0.068
MPC		0.51
ClinPred		0.39	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.071
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-116750787;