9-92847453-C-G

Position:

• chr9-92847453-C-G

Variant summary

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

The ENST00000375495.8(ZNF484):​c.1334G>C​(p.Cys445Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF484 ENST00000375495.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.84

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF484	NM_031486.4	c.1334G>C	p.Cys445Ser	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.1334G>C	p.Cys445Ser	missense_variant	5/5	1	NM_031486.4	ENSP00000364645.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Mar 29, 2022

The c.1334G>C (p.C445S) 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 1334, causing the cysteine (C) at amino acid position 445 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	0.93
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	.;.;T;.
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.40	T;T;T;.
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.70	D;D;D;D
MetaSVM	Uncertain	0.79	D
MutationAssessor	Pathogenic	3.1	.;.;M;.
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-9.3	.;.;D;D
REVEL	Uncertain	0.51
Sift	Pathogenic	0.0	.;.;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.43
MutPred		0.73		.;.;Gain of disorder (P = 0.0097);.;
MVP		0.92
MPC		0.72
ClinPred		1.0	D
GERP RS		2.3
Varity_R		0.88
gMVP		0.15

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: chr9-95609735;