NM_133464.5:c.484C>T

Variant names:

• chr9-111530946-C-T
• rs1447699150
• NM_133464.5:c.484C>T

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.484C>T​(p.Pro162Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.631
• 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=0.055260092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133464.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF483	NM_133464.5	MANE Select	c.484C>T	p.Pro162Ser	missense	Exon 3 of 6	NP_597721.2	Q8TF39-1
	ZNF483	NM_001007169.6		c.484C>T	p.Pro162Ser	missense	Exon 3 of 6	NP_001007170.1	Q8TF39-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF483	ENST00000309235.6	TSL:1 MANE Select	c.484C>T	p.Pro162Ser	missense	Exon 3 of 6	ENSP00000311679.5	Q8TF39-1
	ZNF483	ENST00000355824.7	TSL:1	c.484C>T	p.Pro162Ser	missense	Exon 3 of 6	ENSP00000438048.1	Q6P088
	ZNF483	ENST00000904413.1		c.484C>T	p.Pro162Ser	missense	Exon 4 of 7	ENSP00000574477.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.37
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.094	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.63
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.019
Sift	Benign	0.57	T
Sift4G	Benign	0.73	T
Polyphen		0.044	B
Vest4		0.28
MutPred		0.23		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.13
MPC		1.0
ClinPred		0.076	T
GERP RS		1.7
Varity_R		0.033
gMVP		0.27
Mutation Taster		=98/2	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: rs1447699150; hg19: chr9-114293226;