chr9-92847263-C-G

Position:

• chr9-92847263-C-G

Variant summary

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

The NM_031486.4(ZNF484):​c.1524G>C​(p.Arg508Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF484 NM_031486.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.42

Genes affected

ZNF484 (HGNC:23385): (zinc finger protein 484) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288271 (HGNC:):

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=0.07483488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF484	NM_031486.4	c.1524G>C	p.Arg508Ser	missense_variant	5/5	ENST00000375495.8	NP_113674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF484	ENST00000375495.8	c.1524G>C	p.Arg508Ser	missense_variant	5/5	1	NM_031486.4	ENSP00000364645.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

May 28, 2024

The c.1524G>C (p.R508S) alteration is located in exon 5 (coding exon 4) of the ZNF484 gene. This alteration results from a G to C substitution at nucleotide position 1524, causing the arginine (R) at amino acid position 508 to be replaced by a serine (S). 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	Pathogenic	0.88
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0014	.;.;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.00045	N
LIST_S2	Benign	0.16	T;T;T;.
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.075	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.39	.;.;N;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.2	.;.;N;D
REVEL	Benign	0.13
Sift	Benign	0.12	.;.;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.91	.;.;P;.
Vest4		0.17
MutPred		0.35		.;.;Gain of disorder (P = 0.0672);.;
MVP		0.40
MPC		0.23
ClinPred		0.18	T
GERP RS		2.3
Varity_R		0.22
gMVP		0.11

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: chr9-95609545;