9-111530912-G-C

Variant names:

• chr9-111530912-G-C
• rs200679867
• NM_133464.5:c.450G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133464.5(ZNF483):​c.450G>C​(p.Glu150Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,397,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E150E) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751
• Publications: 0 publications found

Genes affected

ZNF483 (HGNC:23384): (zinc finger protein 483) Predicted to enable DNA-binding transcription factor 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062361866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF483	NM_133464.5	c.450G>C	p.Glu150Asp	missense_variant	Exon 3 of 6	ENST00000309235.6	NP_597721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF483	ENST00000309235.6	c.450G>C	p.Glu150Asp	missense_variant	Exon 3 of 6	1	NM_133464.5	ENSP00000311679.5
ZNF483	ENST00000355824.7	c.450G>C	p.Glu150Asp	missense_variant	Exon 3 of 6	1		ENSP00000438048.1
ZNF483	ENST00000358151.8	c.450G>C	p.Glu150Asp	missense_variant	Exon 3 of 6	2		ENSP00000350871.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1397984 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 695934

African (AFR) AF: 0.0000309 AC: 1 AN: 32376

American (AMR) AF: 0.00 AC: 0 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23928

East Asian (EAS) AF: 0.00 AC: 0 AN: 37698

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5492

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1070114

Other (OTH) AF: 0.00 AC: 0 AN: 56490

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.71
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M;.;M
PhyloP100		0.75
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0050	.;B;B
Vest4		0.23
MutPred		0.12		Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);Gain of loop (P = 0.0502);
MVP		0.30
MPC		0.57
ClinPred		0.10	T
GERP RS		0.61
Varity_R		0.046
gMVP		0.10
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs200679867; hg19: chr9-114293192;