9-111530946-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133464.5(ZNF483):​c.484C>A​(p.Pro162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,774 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P162S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ZNF483 NM_133464.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091511995).

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>A	p.Pro162Thr	missense	Exon 3 of 6	NP_597721.2	Q8TF39-1
	ZNF483	NM_001007169.6		c.484C>A	p.Pro162Thr	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>A	p.Pro162Thr	missense	Exon 3 of 6	ENSP00000311679.5	Q8TF39-1
	ZNF483	ENST00000355824.7	TSL:1	c.484C>A	p.Pro162Thr	missense	Exon 3 of 6	ENSP00000438048.1	Q6P088
	ZNF483	ENST00000904413.1		c.484C>A	p.Pro162Thr	missense	Exon 4 of 7	ENSP00000574477.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD2 exomes AF: 0.00 AC: 0 AN: 241410 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385774 Hom.: 0 Cov.: 25 AF XY: 0.00000145 AC XY: 1 AN XY: 690128

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31954

American (AMR) AF: 0.00 AC: 0 AN: 42248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23836

East Asian (EAS) AF: 0.00 AC: 0 AN: 37330

South Asian (SAS) AF: 0.00 AC: 0 AN: 78646

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061812

Other (OTH) AF: 0.0000179 AC: 1 AN: 55956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.46
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.9	M
PhyloP100		0.63
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.034
Sift	Benign	0.44	T
Sift4G	Benign	0.57	T
Polyphen		0.43	B
Vest4		0.47
MutPred		0.25		Loss of glycosylation at T159 (P = 0.0577)
MVP		0.15
MPC		1.1
ClinPred		0.17	T
GERP RS		1.7
Varity_R		0.049
gMVP		0.27
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: rs1447699150; hg19: chr9-114293226;